Sample records for functionalized linking chains

Agol has conjectured that minimally twisted n-chainlinks are the smallest volume hyperbolic manifolds with n cusps, for n at most 10. In his thesis, Venzke mentions that these cannot be smallest volume for n at least 11, but does not provide a proof. In this paper, we give a proof of Venzke's statement. The proof for n at least 60 is completely rigorous. The proof for n between 11 and 59 uses a computer calculation, and can be made rigorous for manifolds of small enough complexity, using methods of Moser and Milley. Finally, we prove that the n-chainlink with 2m or 2m+1 half-twists cannot be the minimal volume hyperbolic manifold with n cusps, provided n is at least 60 or |m| is at least 8, and we give computational data indicating this remains true for smaller n and |m|.

The paper analyzes effects of geometry on interaction between the chain and chain wheels of face conveyors in underground coal mines. Interaction between chainlinks and wheel toothing is investigated using mathematical models. Three mesh types are comparatively evaluated, so-called normal mesh, nominal mesh and special mesh. Chain position on the chain wheel is shown in 3 schemes. Mathematical formulae used for characterizing mesh types are derived. Effects of the following factors on interaction between a chainlink and a chain wheel are analyzed: link quality and differences in quality and dimensions among chainlinks, friction wear of links and toothing, elastic and plastic chain elongation, friction between links and toothing. A geometric model of the interaction between the chain wheel and haulage chain (in the form of a double polygon) is used. The mathematical model permits the following problems to be analyzed: load distribution among chainlinks on a chain wheel, load distribution on toothing, load fluctuations, effects of friction wear of chain and toothing. Examples of practical use of the formulae are discussed. (14 refs.)

Uses a chain metaphor for describing mentoring, a nurturing process in which an accomplished professional serves as role model, sponsor, master teacher, and career counselor for a promising novice. Suggests that more mentors are needed to encourage others to become or remain technology education teachers. (JOW)

Uses a chain metaphor for describing mentoring, a nurturing process in which an accomplished professional serves as role model, sponsor, master teacher, and career counselor for a promising novice. Suggests that more mentors are needed to encourage others to become or remain technology education teachers. (JOW)

Supply chain collaboration has received increasing attention from scholars and practitioners in recent years. However, our understanding of how enterprise information technology facilitates supply chain collaboration is still very limited, especially with regard to Chinese enterprise ownerships such as state-owned firms, joint-venture firms and local village-owned firms. This paper extends the theory established in enterprise information technology (IT) and supply chain collaboration literature and relates it with coordination in China-linked supply chain. Drawing upon an empirical study from 177 Chinese companies, we provide three major findings: (i) uncovered the importance of leveraging enterprise IT through supply chain collaboration; (ii) identified the relationship between enterprise ownership and enterprise technology use and supply chain collaboration in China-linked supply chain and (iii) illustrated effects of supply chain collaborative activities on operational and market performance.

Issues related to the transportation of coal in Canada were discussed. Coal mines in Alberta and British Columbia are often required to transport their products over 1000 km for export at Pacific ports to countries in Asia or power plants in Ontario. The effectiveness of the supply chain is dependent on the inter-relationships between mine, rail, terminals, and ship transport. Coal customers are typically required to hire shipping companies and nominate vessels for terminals that have contracts with coal suppliers. Mines typically inform railway lines of the amounts of coal that will need to be transported each month. Many railways have increased the amounts of coal they are transporting by using lighter-weight aluminum train cars. Further efficiencies have been realized due to new braking and power distribution technologies in trains. Multiple locomotives are now also being used to provide improved control over the cars that carry the coal. Despite advances in rail technologies, coal deliveries are often delayed by harsh weather conditions and rain. It was concluded that the Canadian coal industry's success relies on its ability to transport large amounts of coal across long distances. 2 figs.

Assembly of two ditopic units, a phenanthroline substituted by 4-ethynyl pyridines at the 2-and 9-positions and a dimetallic paddlewheel, gives a linear chain polymer rather than a closed cyclic species, which would appear equally possible. The chain may be decorated by binding a copper-containing macrocycle around the phenanthroline units to form a polypseudorotaxane. When two phenanthroline ligands are assembled in a first step around copper(I), the paddlewheel acceptor can link them in a second step to form a two-dimensional interwoven grid that resembles the form of a chain-link fence. Each copper(I) centre in this structure is chiral, and the crystal shows complete homochirality, implying selection during the assembly process.

A markerless method is described for tracking the motion of subjects in a three dimensional environment using a model based on linked kinematic chains. The invention is suitable for tracking robotic, animal or human subjects in real-time using a single computer with inexpensive video equipment, and does not require the use of markers or specialized clothing. A simple model of rigid linked segments is constructed of the subject and tracked using three dimensional volumetric data collected by a multiple camera video imaging system. A physics based method is then used to compute forces to align the model with subsequent volumetric data sets in real-time. The method is able to handle occlusion of segments and accommodates joint limits, velocity constraints, and collision constraints and provides for error recovery. The method further provides for elimination of singularities in Jacobian based calculations, which has been problematic in alternative methods.

The CSIRO Mineral Resources Flagship was established to tackle medium- to long-term challenges facing the Australian mineral industry across the value chain from exploration and mining through mineral processing within the framework of an economically, environmentally and socially sustainable minerals industry. This broad portfolio demands collaboration and data exchange with a broad range of participants and data providers across government, research and industry. It is an ideal environment to link geoscience informatics platforms to application across the resource extraction industry and to unlock the value of data integration between traditionally discrete parts of the minerals digital value chain. Despite the potential benefits, data integration remains an elusive goal within research and industry. Many projects use only a subset of available data types in an integrated manner, often maintaining the traditional discipline-based data 'silos'. Integrating data across the entire minerals digital value chain is an expensive proposition involving multiple disciplines and, significantly, multiple data sources both internal and external to any single organisation. Differing vocabularies and data formats, along with access regimes to appropriate analysis software and equipment all hamper the sharing and exchange of information. AuScope has addressed the challenge of data exchange across organisations nationally, and established a national geosciences information infrastructure using open standards-based web services. Federated across a wide variety of organisations, the resulting infrastructure contains a wide variety of live and updated data types. The community data standards and infrastructure platforms that underpin AuScope provide important new datasets and multi-agency links independent of software and hardware differences. AuScope has thus created an infrastructure, a platform of technologies and the opportunity for new ways of working with and integrating

This paper explores and extends the supply chain management strategy for food products effectively and efficiently through analysis of insights to linked partnerships within the supply chain due to the possibility of a global food crisis. The required solution is a collaboration of all parties in the supply chain since an effective supply chain management strategy (ESCMS) for food products is through proper insight between linked partnerships, including customer satisfaction through service q...

The objective of this study was to investigate the effect of chain installation condition on stress distribution that could eventually cause disastrous failure from sudden deformation and geometric rupture. Fractographic method used for the failed chain indicates that over-stress was considered as the root cause of failure. 3D modeling and finite element analysis for the chain, used in a crane hook, were performed with a three-dimensional interactive application program, CATIA, commercial finite element analysis and computational fluid dynamic software, ANSYS. The results showed that the state of stress was changed depending on the initial position of the chain that was installed in the hook. Especially, the magnitude of the stress was strongly affected by the bending forces, which are 2.5 times greater (under the simulation condition currently investigated) than that from the plain tensile load. Also, it was noted that the change of load state is strongly related to the failure of parts. The chain can hold an ultimate load of about 8 tons with only the tensile load acting on it. The conclusions of this research clearly showed that a reduction of the loss from similar incidents can be achieved when an operator properly handles the installation of the chain.

In order to suppress vibration in flexible manipulators, a new type of manipulator mechanism with controllable local degrees of freedom is proposed. This mechanism consists of a main chain and some branch links. The main chain is of a flexible open-chain configuration with an end-effector installed at its tip, and the rigid branch links are able to perform active movements. It is proved by kinematics and dynamic analysis that, the branch links bear no direct kinematic relation to the main chain, but their independent motions can strongly affect the dynamic behavior and performance of the flexible manipulator. Then comes a new idea of suppressing vibration, in which independent motions of the branch links are used to suppress the undesired vibration of the flexible main chain through dynamic coupling. On this basis, an optimal method for reducing vibration of flexible manipulators is proposed. Finally, the effectiveness of this method is verified by numerical simulations.

This commentary compares Centers for Disease Control (CDC) guidelines for vaccine storage with international cold chain standards. Problems related to the use of domestic refrigerators in clinical settings are discussed. Optimal vaccine refrigerator design characteristics are summarized. The adoption of World Health Organization storage recommendations is advised.

Proteus is a multi-mission bus concept developed in partnership by Thales Alenia Space (France) and CNES (France). The first application of this platform was Jason1, an oceanography satellite launched in December 2001. Later on, led by the need for extra power for the next Proteus missions, the initial electrical functionalchain has been modified by the replacement of the previous Nickel-Cadmium battery by a Lithium-ion one, baseline of the new Proteus 5PF platform. The Proteus electrical functionalchain is based on the use of a single battery, permanently connected to the main bus. Its charge is ensured by the on-board software, which adapts the number of solar sections connected the bus. Due to the LEO orbits (700 Km for CALIPSO), the battery is submitted to a high number of cycles (typically 25500 cycles for Calipso). Roughly, a 78Ah nameplate battery, coupled to a solar array delivering 1KW, are able to supply a payload with a power demand up to 600W, for a lifetime higher than three years, under LEO environment. In 2006, on April 28th, the French-American CALIPSO satellite mission has been successfully launched. The CALIPSO mission, project involving NASA (US), CNES (France) and the Institut Pierre-Simon Laplace (CNRS, France), is the first satellite using the Proteus 5PF. CALIPSO provides 3D perspectives of clouds and Aerosols. The second Proteus 5PF mission, the space telescope COROT, has been launched in 2006, on December 27th. COROT is a mission of astronomy led by CNES, in association with CNRS, aimed to detect extra-solar planets. The third Proteus 5PF mission, the oceanography satellite Jason2, has been successfully launched on 2008 June 20th. JASON2 is a fourth-partner mission with NASA, CNES, EUMETSAT and NOAA, whose objective is to continue JASON1 sea surface topography measurements with a goal of improving accuracy to 2.5 centimeters. The fourth Proteus 5PF mission, the scientific earth observation satellite SMOS, has been launched on 2009

Current customs applications are declaration based to support the various customs procedures based on (inter)national laws and regulations. To be able to perform a proper supply chain risk analysis, customs requires to have all data in supply chains. The current declaration procedures are not suffic

textabstractGlobal value chains are driven by considerations of cost and efficiency but just as much by power relations. This appears evident from studies of industrial relations and labour outcomes within value chains, especially those where drivenness is most explicit. Within a context of disaggre

textabstractGlobal value chains are driven by considerations of cost and efficiency but just as much by power relations. This appears evident from studies of industrial relations and labour outcomes within value chains, especially those where drivenness is most explicit. Within a context of

This thesis is divided into two parts. In the first part we focus mainly on certain aspects of the AdS/CFT correspondence. The AdS/CFT correspondence is a proposed duality between Type IIB superstring theory on AdS5 × S5 and N = 4 supersymmetric Yang-Mills theory. In the BMN limit string states located in the center of AdS5 rotate quickly around the equator of the S5 and correspond, in the dual theory, to operators constructed as long chains of sub-operators. This structure of the operators can be formulated as a spin chain and by using the Bethe ansatz their properties can be obtained by solving a set of Bethe equations. Having infinitely many sub-operators, there are methods for solving the Bethe equations in certain sectors. In paper III finite size corrections to the anomalous dimensions in the SU(2) sector are calculated to leading order. Inspired by the chain structure of the corresponding operators, the theory of string bits treats the strings as a discrete sets of points. This theory suffers...

This study demonstrates that the Chinese apple export chains are highly coordinated through ongoing long term loyal network relationships and vertical integration. Various chain governance mechanisms were formed and link small-scale apple farmers in China with export markets. These institutional inn

The influence of conception of total quality management (TQM) on functioning of supply chain is explained. The place of quality of processes and products in the supply chain is identified. Dependence of logistic effects on the level of quality in the supply chain is well-proven.

We propose a nonlocal density functional theory for associating chain molecules. The chains are modeled as tangent spheres, which interact via Lennard-Jones (12,6) attractive interactions. A selected segment contains additional, short-ranged, highly directional interaction sites. The theory incorporates an accurate treatment of the chain molecules via the intramolecular potential formalism and should accurately describe systems with strongly varying external fields, e.g., attractive walls. Within our approach we investigate the structure of the liquid-vapor interface and capillary condensation of a simple model of associating chains with only one associating site placed on the first segment. In general, the properties of inhomogeneous associating chains depend on the association energy. Similar to the bulk systems we find the behavior of associating chains of a given length to be in between that for the nonassociating chains of the same length and that for the nonassociating chains twice as large.

The robustness of ecosystems to species losses is a central question in ecology, given the current pace of extinctions and the many species threatened by human impacts, including habitat destruction and climate change. Robustness from the perspective of secondary extinctions has been addressed in the context of food webs to consider the complex network of species interactions that underlie responses to perturbations. In-silico removal experiments have examined the structural properties of food webs that enhance or hamper the robustness of ecosystems to species losses, with a focus on the role of hubs, the most connected species. Here we take a different approach and focus on the role of the connections themselves. We show that trophic links can be divided into functional and redundant based on their contribution to robustness. The analysis of empirical webs shows that hubs are not necessarily the most important species as they may hold many redundant links. Furthermore, the fraction of functional connections is high and constant across systems regardless of size and interconnectedness. The main consequence of this scaling pattern is that ecosystem robustness can be considerably reduced by species extinctions even when these do not result in any secondary extinctions. This introduces the possibility of tipping points in the collapse of ecosystems.

A long standing problem in information technology security is how to help reduce the security footprint. Many specific proposals exist to address specific problems in information technology security. Most information technology solutions need to be repeatable throughout the course of an information systems lifecycle. The Chain-Link Fence Model is…

A long standing problem in information technology security is how to help reduce the security footprint. Many specific proposals exist to address specific problems in information technology security. Most information technology solutions need to be repeatable throughout the course of an information systems lifecycle. The Chain-Link Fence Model is…

This case study found out how a public-private partnership in Burkina Faso helped female shea nut producers to link up with the cosmetic industry. Empirical data collected from October-December 2011 revealed that the shea value chain partnership between a international shea processing company, a dev

A novel rigorous statistical treatment is applied to available data (May 9, 2016) from search and spectroscopy experiments on the elements with atomic numbers Z = 115 and Z = 117. The present analysis implies that the hitherto proposed cross-reaction link between α-decay chains associated with the isotopes 293117 and 289115 is highly improbable.

A novel rigorous statistical treatment is applied to available data (May 9, 2016) from search and spectroscopy experiments on the elements with atomic numbers Z=115 and Z=117 . The present analysis implies that the hitherto proposed cross-reaction link between α -decay chains associated with the isotopes 293 117 and 289 115 is highly improbable.

Full Text Available A novel rigorous statistical treatment is applied to available data (May 9, 2016 from search and spectroscopy experiments on the elements with atomic numbers Z=115 and Z=117. The present analysis implies that the hitherto proposed cross-reaction link between α-decay chains associated with the isotopes 293117 and 289115 is highly improbable.

Full Text Available Abstract Background The analysis of microarray experiments requires accurate and up-to-date functional annotation of the microarray reporters to optimize the interpretation of the biological processes involved. Pathway visualization tools are used to connect gene expression data with existing biological pathways by using specific database identifiers that link reporters with elements in the pathways. Results This paper proposes a novel method that aims to improve microarray reporter annotation by BLASTing the original reporter sequences against a species-specific EMBL subset, that was derived from and crosslinked back to the highly curated UniProt database. The resulting alignments were filtered using high quality alignment criteria and further compared with the outcome of a more traditional approach, where reporter sequences were BLASTed against EnsEMBL followed by locating the corresponding protein (UniProt entry for the high quality hits. Combining the results of both methods resulted in successful annotation of > 58% of all reporter sequences with UniProt IDs on two commercial array platforms, increasing the amount of Incyte reporters that could be coupled to Gene Ontology terms from 32.7% to 58.3% and to a local GenMAPP pathway from 9.6% to 16.7%. For Agilent, 35.3% of the total reporters are now linked towards GO nodes and 7.1% on local pathways. Conclusion Our methods increased the annotation quality of microarray reporter sequences and allowed us to visualize more reporters using pathway visualization tools. Even in cases where the original reporter annotation showed the correct description the new identifiers often allowed improved pathway and Gene Ontology linking. These methods are freely available at http://www.bigcat.unimaas.nl/public/publications/Gaj_Annotation/.

This thesis analyses consumer acceptance of functional foods and food manufacturers' decision to develop functional foods. The thesis sets up four key research questions: (1) How consumers accept functional foods enriched with omega-3? (2) How the intention of purchasing carrier ingredient...... combinations is explained by general attitudes to functional foods, consumers' health concerns, and the perceived fit of a particular carrier ingredient combination? (3) How food manufacturers decide to develop functional foods? (4) What are the determinants and drivers of food manufacturers' decision...... to develop functional foods? Research question 1 The health benefit of a functional food product is in fact limited if it is not eaten regularly and thus is not part of the healthy diet. For that reason it is highly relevant to look at the dietary change research when studying functional food acceptance...

The objective of this work was to anionically synthesize well-defined polymers having functional groups either at the chain-end or along the polymer chain. General functionalization methods (GFM) were used for synthesizing both kinds of polymers. Chain-end functionalized polymers were synthesized by terminating the anionically synthesized, living polymer chains using chlorodimethylsilane. Hydrosilation reactions were then done between the silyl-hydride groups at the chain-ends and the double bonds of commercially available substituted alkenes. This produced a range of well-defined polymers having the desired functional groups at the chain-ends. In-chainfunctionalized polymers were synthesized by anionically polymerizing a silylhydride functionalized styrene monomer: (4-vinylphenyl)dimethysilane. Polymerizations were done at room temperature in hydrocarbon solvents to produce well-defined polymers. Functional groups were then introduced into the polymer chains by use of hydrosilation reactions done post-polymerization. The functionalized polymers produced were characterized using SEC, 1H and 13C NMR, FTIR, MALDI TOF mass spectrometry and DSC. The monomer reactivity ratios in the copolymerization of styrene with (4-vinylphenyl)dimethylsilane were also measured. A series of copolymerizaions was done with different molar ratios of styrene(S) and (4-vinylphenyl)dimethylsilane(Si). Three different methods were used to determine the values of the monomer reactivity ratios: Fineman-Ross, Kelen-Tudos and Error-In-Variable (EVM) methods. The average values of the two monomer reactivity ratios obtained were: r Si = 0.16 and rS = 1.74. From these values it was observed that in the copolymerization of styrene with (4-vinylphenyl)dimethylsilane, the second monomer was preferentially incorporated into the copolymer chain. Also, rSirS = 0.27, which shows that the copolymer has a tendency to have an alternating structure. Amino acid-functionalized polymers (biohybrids) were

... (as indicated by the large number of X-linked mental retardation syndromes). In addition, there is evidence for relatively specific effects of X-linked genes on social-cognition and emotional regulation...

Full Text Available A theory of a generalized form of the chain transforms of order n is developed, and various properties of these are established including the Parseval relation. Most known cases of the standard theory are derived as special cases. Also a theory of self-reciprocal functions is given, based on these general chain transforms; and relations among various classes of self-reciprocal functions are established.

Extracellular neuritic plaques, composed of aggregated amyloid-β (Aβ) peptides, are one of the major histopathological hallmarks of Alzheimer's disease (AD), a progressive, irreversible neurodegenerative disorder and the most common cause of dementia in the elderly. One of the most prominent risk factor for sporadic AD, carrying one or two aberrant copies of the apolipoprotein E (ApoE) ε4 alleles, closely links AD to lipids. Further, several lipid classes and fatty acids have been reported to be changed in the brain of AD-affected individuals. Interestingly, the observed lipid changes in the brain seem not only to be a consequence of the disease but also modulate Aβ generation. In line with these observations, protective lipids being able to decrease Aβ generation and also potential negative lipids in respect to AD were identified. Mechanistically, Aβ peptides are generated by sequential proteolytic processing of the amyloid precursor protein (APP) by β- and γ-secretase. The α-secretase appears to compete with β-secretase for the initial cleavage of APP, preventing Aβ production. All APP-cleaving secretases as well as APP are transmembrane proteins, further illustrating the impact of lipids on Aβ generation. Beside the pathological impact of Aβ, accumulating evidence suggests that Aβ and the APP intracellular domain (AICD) play an important role in regulating lipid homeostasis, either by direct effects or by affecting gene expression or protein stability of enzymes involved in the de novo synthesis of different lipid classes. This review summarizes the current literature addressing the complex bidirectional link between lipids and AD and APP processing including lipid alterations found in AD post mortem brains, lipids that alter APP processing and the physiological functions of Aβ and AICD in the regulation of several lipid metabolism pathways.

Wormlike or threadlike structures with local cylindrical geometry are abundantly found in nature and technical products. A thorough structural characterization in the bulk for a whole ensemble, however, is difficult. The inherent semiordered nature of the tortuous large-scale structure and especially the quantification of branching renders an assessment difficult. In the present work we introduce a hybrid function expressing the scattering intensities for X-rays, neutrons, or light in the small-angle regime for this system. The function is termed "hybrid" because it employs terms from different approaches. The large-scale structure is described via a Guinier term as well as a concomitant power-law expression in momentum transfer q taken from the so-called unified function. The local cylindrical shape, however, is taken into account through a form factor for cylinders from rigid-body modeling. In principle, the latter form factor can be replaced by an expression for any other regular body so that the new hybrid function is a versatile tool for studying hierarchical structures assembled from uniform subunits. The appropriateness and capability of the new function for cylindrical structures is exemplified using the example of a wormlike micellar system.

A long standing problem in information technology security is how to help reduce the security footprint. Many specific proposals exist to address specific problems in information technology security. Most information technology solutions need to be repeatable throughout the course of an information systems lifecycle. The Chain-Link Fence Model is a new model for creating and implementing information technology procedures. This model was validated by two different methods: the first being int...

Transduction of exogenous T-cell receptor (TCR) genes into patients' activated peripheral blood T cells is a potent strategy to generate large numbers of specific T cells for adoptive therapy of cancer and viral diseases. However, the remarkable clinical promise of this powerful approach is still being overshadowed by a serious potential consequence: mispairing of the exogenous TCR chains with endogenous TCR chains. These 'mixed' heterodimers can generate new specificities that result in graft-versus-host reactions. Engineering TCR constant regions of the exogenous chains with a cysteine promotes proper pairing and reduces the mispairing, but, as we show here, does not eliminate the formation of mixed heterodimers. By contrast, deletion of the constant regions, through use of a stabilized Vα/Vβ single-chain TCR (scTv), avoided mispairing completely. By linking a high-affinity scTv to intracellular signaling domains, such as Lck and CD28, the scTv was capable of activating functional T-cell responses in the absence of either the CD3 subunits or the co-receptors, and circumvented mispairing with endogenous TCRs. Such transduced T cells can respond to the targeted antigen independent of CD3 subunits via the introduced scTv, without the transduced T cells acquiring any new undefined and potentially dangerous specificities.

Full Text Available To reduce waste and wastewater pollution and to improve the utilization rate of resources in the pig-industry chain, a circular economy of the chain can be developed. The key to constructing the circular economic system of the pig-industry chain is to determine the path of the cyclic materials and to design reasonable waste- and wastewater-treatment capacities. This paper focuses on the treatment and recycling of wastewater in the pig-industry chain and the treatment and recycling of waste into manure and feed. After giving the two circular paths, the paper proposes a multi-objective uncertainty-optimization model for the cyclic links of the pig-industry chain with the highest resource-reuse efficiency and the lowest construction cost based on the uncertainty of market demand. Using a combination of the neural network and genetic algorithm method for designing the solution process for the model, the paper finally introduces the determination methods of relevant parameters and verifies the feasibility and effectiveness of the model through a case study.

A classical harmonic diatomic chain is studied using the recurrence relations method. The momentum autocorrelation function results from contributions of acoustic and optical branches. By use of convolution theorem, analytical expressions for the acoustic and optical contributions are derived as even-order Bessel function expansions with coefficients given in terms of integrals of elliptic functions in real axis and a contour parallel to the imaginary axis, respectively. - Highlights: • Momentum autocorrelation function of a classic diatomic chain is studied. • It is derived as even-order Bessel function expansion using the convolution theorem. • The expansion coefficients are integrals of elliptic functions. • Addition theorem is used to reduce complex elliptic function to complex sum of real ones.

The coordination problem of a supply chain comprising one supplier and one retailer under market demand disruption is studied in this article. A novel exponential demand function is adopted, and the penalty cost is introduced explicitly to capture the deviation production cost caused by the market demand disruption. The optimal strategies are obtained for different disruption scale under the centralized mode. For the decentralized mode, it is proved that the supply chain can be fully coordinated by adjusting the price discount policy appropriately when disruption occurs. Furthermore, the authors point out that similar results can be established for more general demand functions that represent different market circumstances if certain assumptions are satisfied.

Tctex1 and Tctex2 were originally described as potential distorters/sterility factors in the non-Mendelian transmission of t-haplotypes in mice. These proteins have since been identified as subunits of cytoplasmic and/or axonemal dyneins. Within the Chlamydomonas flagellum, Tctex1 is a subunit of inner arm I1. We have now identified a second Tctex1-related protein (here termed LC9) in Chlamydomonas. LC9 copurifies with outer arm dynein in sucrose density gradients and is missing only in those strains completely lacking this motor. Zero-length cross-linking of purified outer arm dynein indicates that LC9 interacts directly with both the IC1 and IC2 intermediate chains. Immunoblot analysis revealed that LC2, LC6, and LC9 are missing in an IC2 mutant strain (oda6-r88) that can assemble outer arms but exhibits significantly reduced flagellar beat frequency. This defect is unlikely to be due to lack of LC6, because an LC6 null mutant (oda13) exhibits only a minor swimming abnormality. Using an LC2 null mutant (oda12-1), we find that although some outer arm dynein components assemble in the absence of LC2, they are nonfunctional. In contrast, dyneins from oda6-r88, which also lack LC2, retain some activity. Furthermore, we observed a synthetic assembly defect in an oda6-r88 oda12-1 double mutant. These data suggest that LC2, LC6, and LC9 have different roles in outer arm assembly and are required for wild-type motor function in the Chlamydomonas flagellum. PMID:16195342

To investigate the relationship between the biological activity of recombined single chain insulin and the length of the connecting peptide, we designed and prepared three single chain insulin molecules, namely, PIP, [A]5PIP and [A]10PIP, by site-directed mutagenesis, in which B30 and A1 were linked through dipeptide A-K, heptapeptide A-A-A-A-A-A-K, and dodecapeptide A-A-A-A-A-A-A-A-A-A-A-K, respectively. Their receptor binding capacities were 0.14%, 14.3% and 11.1% of that of insulin respectively and their in vivo biological activities were in consistence with their receptor binding capacity; whereas their growth promoting activities were 17%, 116.3% and 38% of that of insulin. These results suggested the following conclusions. (i) The recombined single chain insulin could also possess the same metabolic and mitogenic function as insulin. (ii) The receptor binding capacity of recombined single chain insulin to insulin receptor was closely related to the length and amino acid composition of the connecting peptide and could change from 0 to 100% of insulin depending on the different connecting peptides. This result further illustrated the necessity of B chain C-terminus swaying away from A chain N-terminus when insulin binds to its receptor. (iii) The mitogenic activity of recombined single chain insulin also depended on the length and the amino acid composition of the connecting peptide and was higher than its metabolic activity.

The multi-functionality of microwave links based on remote heterodyne detection of signals from a dual-frequency laser transmitter is discussed and experimentally demonstrated in this paper. Typically, direct detection in conjunction with optical intensity modulation is used to implement fibre......-optic microwave links. The resulting links are inherently transparent and mainly used for signal transmission. As opposed to direct detection links, remote heterodyne detection links can directly perform functionalities such as modulation, frequency conversion, and transparent signal recovery in addition...

Irradiated, thermally stabilized, highly cross-linked UHMWPE bearings have demonstrated superior wear performance and improved in vitro oxidation resistance compared with terminally gamma-sterilized bearings, yet retrieval analysis reveals unanticipated in vivo oxidation in these materials despite fewer or no measurable free radicals. There has been little evidence to date that the oxidation mechanism in thermally stabilized materials is the same as that in conventional materials, and so it is unknown whether oxidation in these materials is leading to chain scission and a degradation of mechanical properties, molecular weight, and crosslink density. The aim of this study was to determine whether measured in vivo oxidation in retrieved, highly cross-linked tibial bearings corresponds with a decreasing crosslink density. Analysis of three tibial bearing materials revealed that crosslink density decreased following in vivo duration, and that the change in crosslink density was strongly correlated with oxidation. The results suggest that oxidation in highly cross-linked materials is causing chain scissions that may, in time, impact the material properties. If in vivo oxidation continues over longer durations, there is potential for a clinically significant degradation of mechanical properties.

Previous studies with concurrent-chains procedures have shown that preference for a terminal-link signaling a higher reinforcement rate decreases as initial-link durations increase. Using a concurrent-chains procedure, the present experiment examined the effects of manipulating initial-link duration on preference and resistance to disruption with rats nose poking for different rates of food reinforcement in the terminal links. Consistent with previous findings, preference for a terminal link with a higher reinforcement rate decreased with longer initial links. Conversely, relative resistance to disruption in the terminal link with a higher reinforcement rate increased with longer initial links. These findings are counter to the prediction of behavioral momentum theory that preference and resistance to change should be positively related.

The covalent attachment of different types of poly-ubiquitin chains signal different outcomes for the proteins so targeted. For example, a protein modified with Lys-48-linked poly-ubiquitin chains is targeted for proteasomal degradation, whereas Lys-63-linkedchains encode nondegradative signals. The structural features that enable these different types of chains to encode different signals have not yet been fully elucidated. We report here the X-ray crystal structures of Lys-63-linked tri- and di-ubiquitin at resolutions of 2.3 and 1.9 {angstrom}, respectively. The tri- and di-ubiquitin species adopt essentially identical structures. In both instances, the ubiquitin chain assumes a highly extended conformation with a left-handed helical twist; the helical chain contains four ubiquitin monomers per turn and has a repeat length of {approx}110 {angstrom}. Interestingly, Lys-48 ubiquitin chains also adopt a left-handed helical structure with a similar repeat length. However, the Lys-63 architecture is much more open than that of Lys-48 chains and exposes much more of the ubiquitin surface for potential recognition events. These new crystal structures are consistent with the results of solution studies of Lys-63 chain conformation, and reveal the structural basis for differential recognition of Lys-63 versus Lys-48 chains.

We present calculations of charm and beauty production at Tevatron within the framework of k{sub T} -factorization, using the unintegrated gluon distributions as obtained from the Linked Dipole Chain model. The analysis covers transverse momentum and rapidity distributions and the azimuthal correlations between b and b-bar quarks (or rather muons from their decay) which are powerful tests for the different unintegrated gluon distributions. We compare the theoretical results with recent experimental data taken by D{phi} and CDF collaborations at the Tevatron Run I and II. (author)

Full Text Available This article links key findings from two major research literatures within contemporary development and globalization studies: global commodity/value chains, and world income inequalities. Forging this missing link exposes what I call the upgrading paradox within commodity and value chain analysis. The paradox hinges on the disconnect between the global commodity/value chain literatures focus on the potential for firms and nations to upgrade their position within chains and the roots of the global commodity chain construct in world-systems analysis, a theoretical framework that rejects the potential for widespread and generalizable developmental progress. Findings from the world income inequalities literature do indeed confirm the paradoxical nature of the upgrading discourse, so I conclude by discussing two potential paths for a post-paradox commodity chain analysis.

Full Text Available The calculation of the correlation functions of Bethe ansatz solvable models is very difficult problem. Among these solvable models spin 1/2 XXX chain has been investigated for a long time. Even for this model only the nearest neighbor and the second neighbor correlations were known. In 1990's multiple integral formula for the general correlations is derived. But the integration of this formula is also very difficult problem. Recently these integrals are decomposed to products of one dimensional integrals and at zero temperature, zero magnetic field and isotropic case, correlation functions are expressed by log 2 and Riemann's zeta functions with odd integer argument ς(3,ς(5,ς(7,.... We can calculate density sub-matrix of successive seven sites. Entanglement entropy of seven sites is calculated. These methods can be extended to XXZ chain up to n=4. Correlation functions are expressed by the generalized zeta functions. Several years ago I derived new thermodynamic Bethe ansatz equation for XXZ chain. This is quite different with Yang-Yang type TBA equations and contains only one unknown function. This equation is very useful to get the high temperature expansion. In this paper we get the analytic solution of this equation at Δ=0.

The RING E3 ligase catalysed formation of lysine 63 linked ubiquitin chains by the Ube2V2–Ubc13 E2 complex is required for many important biological processes. Here we report the structure of the RING domain dimer of rat RNF4 in complex with a human Ubc13~Ub conjugate and Ube2V2. The structure has captured Ube2V2 bound to the acceptor (priming) ubiquitin with Lys63 in a position that could lead to attack on the linkage between the donor (second) ubiquitin and Ubc13 that is held in the active “folded back” conformation by the RING domain of RNF4. The interfaces identified in the structure were verified by in vitro ubiquitination assays of site directed mutants. This represents the first view of the synthesis of Lys63 linked ubiquitin chains in which both substrate ubiquitin and ubiquitin-loaded E2 are juxtaposed to allow E3 ligase mediated catalysis. PMID:26148049

Full Text Available Concepts like supply chain network complexity, interdependence and risk assessment have been prominently discussed directly and indirectly in management literature over past decades and plenty of frameworks and conceptual prescriptive research works have been published contributing towards building the body of knowledge. However previous studies often lacked quantification of the findings. Consequently, the need for suitable scales becomes prominent for measuring those constructs to empirically support the conceptualized relationships. This paper expands the understanding of supply chain network complexity (SCNC and also highlights its implications on interdependence (ID between the actors and risk assessment (RAS in transaction relationships. In doing so, SCNC and RAS are operationalized to understand how SCNC affects interdependence and risk assessment between the actors in the supply chain network. The contribution of this study lies in developing and validating multi-item scales for these constructs and empirically establishing the hypothesized relationships in the Indian context based on firm data collected using survey–based questionnaire. The methodology followed included structural equation modeling. The study findings indicate that SCNC had significant relationship with interdependence, which in turn significantly affected risk assessment. This study carries both academic and managerial implications and provides an empirically supported framework linking network complexity with the two key variables (ID and RAS, playing crucial roles in managerial decision making. This study contributes to the body of knowledge and aims at guiding managers in better understanding transaction relationships.

This thesis is meant to global companies that would implement purchasing and logistics strategies in order to win a competitive edge and increase their performance. The purpose of this thesis is to learn about the organization of purchasing and logistics functions within global companies. Not only to discover their organization but also to understand their operational principal and realize how strategic and important those function can be to an international company. The Case Stu...

The contribution of supramolecular chemistry to polymer science opens new perspectives for the design of polymer materials exhibiting valuable properties and easier processability due to the dynamic nature of non-covalent interactions. Hydrogen bonding polymers can be used as supramolecular units for yielding larger assemblies that possess attractive features, arising from the combination of polymer properties and the responsiveness of hydrogen bonds. The post-polymerization modification of reactive end-groups is the most common procedure for generating such polymers. Examples of polymerizations mediated by hydrogen bonding-functionalized precursors have also recently been reported. This contribution reviews the current synthetic routes toward hydrogen bonding sticker chain-end functionalized polymers.

This paper presents a modular photovoltaic system (MPVS) that uses a chain-link-type multilevel converter (CLMC). In large-scale PV generating systems, the DC power supply is generally composed of a large number of PV panels. Hence, losses are caused by differences in the maximum power point at each PV panel. An MPVS has been proposed to address the above mentioned problem. It helps improve the photoelectric conversion efficiency by applying maximum power point tracking (MPPT) control to each group of PV panels. In addition, if a CLMC is used in an MPVS, a high voltage can be output from the AC side and transmission losses can be decreased. However, with this circuit configuration, the current output from the AC side may be unbalanced. Therefore, we propose a method to output balanced current from the AC side, even if the output of the DC power supply is unbalanced. The validity of the proposed method is examined by digital simulation.

Full Text Available The resistance force of the granular matter is modeled as a linear superposition of a static (quadratic depth-dependent resistance force and a dynamic (quadratic velocity-dependent frictional force. The impact is defined from the moment the end point of the system comes in contact with the granular matter surface until the vertical linear velocity of the end point is zero. The variables of interest are the final depth at the end of the penetration phase and the stopping time. The results for a two-link kinematic chain with two points of contact were compared to the results obtained by applying the resistance force formulation developed to corresponding CAD simulation models. The results revealed that the final displacement increases with initial velocity, while the stopping time decreases. The sensitivity to the initial velocity was studied and an improvement to the resistance force formulated as a result. A series of expressions are proposed for the resistance force coefficients.

A biomechanics model of six-link kinematic chain of human body is developed by using Kane's method. The kinematic data comprise of six segments; foot, calf, thigh, trunk, upper arm and forearm, are obtained through data collection of walking, running and jumping using the Vicon Nexus system. The motion capture system uses 12 Vicon MX-3+ cameras and 12 Vicon MX-F40 cameras, two DV (50 Hz) cameras and a force plate (100 Hz). Inverse dynamics approach is used to obtain the unknown value of torques produced by joint segments during walking, running and jumping activities. The results show that the largest value of torques produced occurs at the foot segment.

Full Text Available Supply chain management and closed-loop supply chain management (CLSCM have developed into established concepts in recent years. The related material cycles and product returns form an important part of all related processes with high potential for reducing environmental burden. The paper proposes a framework for (environmentally triggered closed-loop supply chain management, spanning three different levels: the societal or governance, the chain and the actor level. Within each level, a set of activities or processes can be identified. Taken together, the levels allow a comprehensive analysis of a closed-loop supply chain system. This is illustrated building on two case studies in the textile and apparel industry, where closed-loop supply chains have been designed to take specific apparel products back. The case studies are analyzed against all three levels and allow exemplification of related challenges and interrelations among the three levels. The three levels contribute to the further comprehension of the multiple issues having to be taken into account for successfully implementing closed-loop supply chains.

We study the spectrum of the integrable open XXX Heisenberg spin chain subject to non-diagonal boundary magnetic fields. The spectral problem for this model can be formulated in terms of functional equations obtained by separation of variables or, equivalently, from the fusion of transfer matrices. For generic boundary conditions the eigenvalues cannot be obtained from the solution of finitely many algebraic Bethe equations. Based on careful finite size studies of the analytic properties of the underlying hierarchy of transfer matrices we devise two approaches to analyze the functional equations. First we introduce a truncation method leading to Bethe-type equations determining the energy spectrum of the spin chain. In a second approach, the hierarchy of functional equations is mapped to an infinite system of nonlinear integral equations of TBA type. The two schemes have complementary ranges of applicability and facilitate an efficient numerical analysis for a wide range of boundary parameters. Some data are presented on the finite-size corrections to the energy of the state which evolves into the antiferromagnetic ground state in the limit of parallel boundary fields.

We study the spectrum of the integrable open XXX Heisenberg spin chain subject to non-diagonal boundary magnetic fields. The spectral problem for this model can be formulated in terms of functional equations obtained by separation of variables or, equivalently, from the fusion of transfer matrices. For generic boundary conditions the eigenvalues cannot be obtained from the solution of finitely many algebraic Bethe equations. Based on careful finite size studies of the analytic properties of the underlying hierarchy of transfer matrices we devise two approaches to analyze the functional equations. First we introduce a truncation method leading to Bethe-type equations determining the energy spectrum of the spin chain. In a second approach, the hierarchy of functional equations is mapped to an infinite system of nonlinear integral equations of TBA type. The two schemes have complementary ranges of applicability and facilitate an efficient numerical analysis for a wide range of boundary parameters. Some data are presented on the finite-size corrections to the energy of the state which evolves into the antiferromagnetic ground state in the limit of parallel boundary fields.

The term executive function is used increasingly within developmental psychology and is often taken to refer to unfolding brain processes. We trace the origins of research on executive function to show that the link with social interaction has a long history. We suggest that a recent frenzy of research exploring methods for studying individual…

The term executive function is used increasingly within developmental psychology and is often taken to refer to unfolding brain processes. We trace the origins of research on executive function to show that the link with social interaction has a long history. We suggest that a recent frenzy of research exploring methods for studying individual…

Full Text Available Supply Chain Management can be seen as a way to achieve integration of all corporate functions. In practice, Supply Chain Management is complex and characterized by numerous activities spread over multiple functions and organizations, which pose challenges to reach effective implementation. Based on literature review, the objective of this paper is to present the theoretical indications regarding professional profile recommended for the Supply Chain Management and discuss the role of these professionals in cross-functional business processes. The literature review demonstrated a growing interest in the thematic, especially because the “soft” aspects (human and behavioral to achieve supply chain internal and external integration. All functions must be involved in Supply Chain Management and supply chain managers have a critical role to play: challenge the supremacy of functions in the organizational structure, implementing the practice of "horizontal work" through cross-functional teams. Overall, this research contributes to academic and practical professionals by the description of the job profile of the supply chain managers and presentation of forms to achieve internal integration.

Full Text Available Nowadays, finely controlling the mechanical properties of polymeric materials is possible by incorporating supramolecular motifs into their architecture. In this context, the synthesis of a side-chain terpyridine-functionalized poly(2-(dimethylaminoethyl methacrylate is reported via reversible addition-fragmentation chain transfer polymerization. By addition of transition metal ions, concentrated aqueous solutions of this polymer turn into metallo-supramolecular hydrogels whose dynamic mechanical properties are investigated by rotational rheometry. Hence, the possibility for the material to relax mechanical constrains via dissociation of transient cross-links is brought into light. In addition, the complex phenomena occurring under large oscillatory shear are interpreted in the context of transient networks.

The literature acknowledges that the type and the level of supply chain integration differ in various situations. This paper investigates the influence of business conditions on internal and external information sharing and the role of ICT in order processing, using a multi-case study among SMEs. Th

The literature acknowledges that the type and the level of supply chain integration differ in various situations. This paper investigates the influence of business conditions on internal and external information sharing and the role of ICT in order processing, using a multi-case study among SMEs.

In 2006, the Public Interest Energy Research Program (PIER) Demand Response Research Center (DRRC) at Lawrence Berkeley National Laboratory initiated research into Automated Demand Response (OpenADR) applications in California industry. The goal is to improve electric grid reliability and lower electricity use during periods of peak demand. The purpose of this research is to begin to define the relationship among a portfolio of actions that industrial facilities can undertake relative to their electricity use. This 'electricity value chain' defines energy management and demand response (DR) at six levels of service, distinguished by the magnitude, type, and rapidity of response. One element in the electricity supply chain is OpenADR, an open-standards based communications system to send signals to customers to allow them to manage their electric demand in response to supply conditions, such as prices or reliability, through a set of standard, open communications. Initial DRRC research suggests that industrial facilities that have undertaken energy efficiency measures are probably more, not less, likely to initiate other actions within this value chain such as daily load management and demand response. Moreover, OpenADR appears to afford some facilities the opportunity to develop the supporting control structure and to 'demo' potential reductions in energy use that can later be applied to either more effective load management or a permanent reduction in use via energy efficiency. Under the right conditions, some types of industrial facilities can shift or shed loads, without any, or minimal disruption to operations, to protect their energy supply reliability and to take advantage of financial incentives. In 2007 and 2008, 35 industrial facilities agreed to implement OpenADR, representing a total capacity of nearly 40 MW. This paper describes how integrated or centralized demand management and system-level network controls are linked to Open

In 2006, the Public Interest Energy Research Program (PIER) Demand Response Research Center (DRRC) at Lawrence Berkeley National Laboratory initiated research into Automated Demand Response (OpenADR) applications in California industry. The goal is to improve electric grid reliability and lower electricity use during periods of peak demand. The purpose of this research is to begin to define the relationship among a portfolio of actions that industrial facilities can undertake relative to their electricity use. This ?electricity value chain? defines energy management and demand response (DR) at six levels of service, distinguished by the magnitude, type, and rapidity of response. One element in the electricity supply chain is OpenADR, an open-standards based communications system to send signals to customers to allow them to manage their electric demand in response to supply conditions, such as prices or reliability, through a set of standard, open communications. Initial DRRC research suggests that industrial facilities that have undertaken energy efficiency measures are probably more, not less, likely to initiate other actions within this value chain such as daily load management and demand response. Moreover, OpenADR appears to afford some facilities the opportunity to develop the supporting control structure and to"demo" potential reductions in energy use that can later be applied to either more effective load management or a permanent reduction in use via energy efficiency. Under the right conditions, some types of industrial facilities can shift or shed loads, without any, or minimal disruption to operations, to protect their energy supply reliability and to take advantage of financial incentives.1 In 2007 and 2008, 35 industrial facilities agreed to implement OpenADR, representing a total capacity of nearly 40 MW. This paper describes how integrated or centralized demand management and system-level network controls are linked to OpenADR systems. Case studies

The green anole, Anolis carolinensis (ACA), is the model reptile for a vast array of biological disciplines. It was the first nonavian reptile to have its genome fully sequenced. During the genome project, the XX/XY system of sex chromosomes homologous to chicken chromosome 15 (GGA15) was revealed, and 106 X-linked genes were identified. We selected 38 genes located on eight scaffolds in ACA and having orthologs located on GGA15, then tested their linkage to ACA X chromosome by using comparative quantitative fluorescent real-time polymerase chain reaction applied to male and female genomic DNA. All tested genes appeared to be X-specific and not present on the Y chromosome. Assuming that all genes located on these scaffolds should be localized to the ACA X chromosome, we more than doubled the number of known X-linked genes in ACA, from 106 to 250. While demonstrating that the gene content of chromosome X in ACA and GGA15 is largely conserved, we nevertheless showed that numerous interchromosomal rearrangements had occurred since the splitting of the chicken and anole evolutionary lineages. The presence of many ACA X-specific genes localized to distinct contigs indicates that the ACA Y chromosome should be highly degenerated, having lost a large amount of its original gene content during evolution. The identification of novel genes linked to the X chromosome and absent on the Y chromosome in the model lizard species contributes to ongoing research as to the evolution of sex determination in reptiles and provides important information for future comparative and functional genomics.

Full Text Available In this article we propose a methodology for estimating the GDP of a country’s different regions, providing quarterly profiles for the annual official observed data. Thus the article offers a new instrument for short-term monitoring that allows the analysts to quantify the degree of synchronicity among regional business cycles. Technically, we combine time-series models with benchmarking methods to process short-term quarterly indicators and to estimate quarterly regional GDPs ensuring their temporal and transversal consistency with the National Accounts data. The methodology addresses the issue of nonadditivity, explicitly taking into account the transversal constraints imposed by the chain-linked volume indexes used by the National Accounts, and provides an efficient combination of structural as well as short-term information. The methodology is illustrated by an application to the Spanish economy, providing real-time quarterly GDP estimates, that is, with a minimum compilation delay with respect to the national quarterly GDP. The estimated quarterly data are used to assess the existence of cycles shared among the Spanish regions.

The plasma membrane glycoproteins of calf thymocytes were converted to glycopeptides by exhaustive pronase digestion. Glycopeptides with asparagine-linked sugar chains were separated from those with mucine-type sugar chains by Bio-Gel P-10 column chromatography. The asparagine-linked sugar chains were released as oligosaccharides from the peptide moiety by hydrazinolysis and labeled by reduction with NaB[3H]4. The radioactive oligosaccharides were fractionated into fifteen acidic components and ten neutral components by combination of paper electrophoresis and Bio-Gel P-4 column chromatography. The acidic nature of all fifteen acidic components can be ascribed to their N-acetylneuraminic acid residues. The Bio-Gel P-4 column chromatographic patterns of the neutral oligosaccharide fraction and of the neutral fraction obtained on sialidase treatment of the pooled acidic oligosaccharide fraction were totally different, indicating that the acidic oligosaccharides are not simple sialyl derivatives of the neutral oligosaccharides.

The configurational properties of tail-like polymer chains with one end attached to a flat surface are studied by using p(z) can be scaled approximately by a factor β to be a length independent function for both random walking (RW) and scaled P(Rz) of the SAW chain roughly overlaps that of the RW chain, but the scaled p(z) of the SAW chain locates at smaller βz than that of the RW chain.

The concepts of random Markov matrix, Markov branching chain in random environment (MBCRE) and Laplace functional of Markov branching chain in random environment (LFMBCRE) are introduced. The properties of LFMBCRE and the explicit formulas of moments of MBCRE are given.

dimensional-space where linear separability is possible. Moreover, the proposed HCFLNN combines the best attribute of particle swarm optimization (PSO, back propagation learning (BP learning, and functionallink neural networks (FLNNs. The proposed method eliminates the need of hidden layer by expanding the input patterns using Chebyshev orthogonal polynomials. We have shown its effectiveness of classifying the unknown pattern using the publicly available datasets obtained from UCI repository. The computational results are then compared with functionallink neural network (FLNN with a generic basis functions, PSO-based FLNN, and EFLN. From the comparative study, we observed that the performance of the HCFLNN outperforms FLNN, PSO-based FLNN, and EFLN in terms of classification accuracy.

The incorporation of Al and increased curing temperature promotes the crystallization and cross-linking of calcium (alumino)silicate hydrate (C-(A-)S-H), which is the primary binding phase in most contemporary concrete materials. However, the influence of Al-induced structural changes on the mechanical properties at atomistic scale is not well understood. Herein, synchrotron radiation-based high-pressure X-ray diffraction is used to quantify the influence of dreierketten chain cross-linking on the anisotropic mechanical behavior of C-(A-)S-H. We show that the ab-planar stiffness is independent of dreierketten chain defects, e.g. vacancies in bridging tetrahedra sites and Al for Si substitution. The c-axis of non-cross-linked C-(A-)S-H is more deformable due to the softer interlayer opening but stiffens with decreased spacing and/or increased zeolitic water and Ca2+ of the interlayer. Dreierketten chain cross-links act as ‘columns’ to resist compression, thus increasing the bulk modulus of C-(A-)S-H. We provide the first experimental evidence on the influence of the Al-induced atomistic configurational change on the mechanical properties of C-(A-)S-H. Our work advances the fundamental knowledge of C-(A-)S-H on the lowest level of its hierarchical structure, and thus can impact the way that innovative C-(A-)S-H-based cementitious materials are developed using a ‘bottom-up’ approach.

Full Text Available In this study, a method of artificial neural network applied for the solution of inverse kinematics of 2-link serial chain manipulator. The method is multilayer perceptrons neural network has applied. This unsupervised method learns the functional relationship between input (Cartesian space and output (joint space based on a localized adaptation of the mapping, by using the manipulator itself under joint control and adapting the solution based on a comparison between the resulting locations of the manipulator's end effectors in Cartesian space with the desired location. Even when a manipulator is not available; the approach is still valid if the forward kinematic equations are used as a model of the manipulator. The forward kinematic equations always have a unique solution, and the resulting Neural net can be used as a starting point for further refinement when the manipulator does become available. Artificial neural network especially MLP are used to learn the forward and the inverse kinematic equations of two degrees freedom robot arm. A set of some data sets were first generated as per the formula equation for this the input parameter X and Y coordinates in inches. Using these data sets was basis for the training and evaluation or testing the MLP model. Out of the sets data points, maximum were used as training data and some were used for testing for MLP. Backpropagation algorithm was used for training the network and for updating the desired weights. In this work epoch based training method was applied.

The standard approach to the general rules for differentiation is to first derive the power, product, and quotient rules and then derive the chain rule. In this short article we give an approach to these rules which uses the chain rule as the main tool in deriving the power, product, and quotient rules in a manner which is more student-friendly…

Full Text Available National statistical agencies of European Union use chain-linking method to achieve the best possible decomposition of GDP. The main advantage of this method is its simplicity, thus it can be applied in practice, which makes it particularly attractive in the situation when GDP has to be compiled on due time. By this method transformation-substitution effect – inherent to rational producers and consumers, has been implicitly built into GDP compilation, which is prior assumption of normative economic theory. On empirical (ex-post ground it gives more precise volume-price decomposition. In this paper, by means of constructing LMTF index and Fisher index derived from the previous one, it is suggested how to improve chainlinking method, due to following reasons: a it is theoretically restrictive, b it gives only rough GDP decomposition into volume and price and, what seems to be its main disadvantage, c it gives additively inconsistent GDP.

We analyze N = 1 theories on S5 and S4 x S1, showing how their partition functions can be written in terms of a set of fundamental 5d holomorphic blocks. We demonstrate that, when the 5d mass parameters are analytically continued to suitable values, the S5 and S4 x S1 partition functions degenerate to those for S3 and S2 x S1. We explain this mechanism via the recently proposed correspondence between 5d partition functions and correlators with underlying q-Virasoro symmetry. From the q-Virasoro 3-point functions, we axiomatically derive a set of associated reflection coefficients, and show they can be geometrically interpreted in terms of Harish-Chandra c-functions for quantum symmetric spaces. We then link these particular c-functions to the types appearing in the Jost functions encoding the asymptotics of the scattering in integrable spin chains, obtained taking different limits of the XYZ model to XXZ-type.

The purpose of this paper is to investigate the impact of switching harmonics on the instantaneous power that flows in the cells of a chain-link based STATCOM when using Phase-Shifted PWM. Two different cases are investigated for the converter cells: low, and high switching frequency. It is shown...... distribution among cells of the same phase leg, thus contributing to the capacitors balancing. Theoretical conclusions are validated through PSCAD simulation results....

We consider a class of continuous time Markov chains on $\\Z^d$. These chains are the discrete space analogue of Markov processes with jumps. Under some conditions, we show that harmonic functions associated with these Markov chains are H\\"{o}lder continuous.

The scope of this study is to establish the significance of human resource practices in reaching high levels of supply chain management performance through the comparison of two companies that belong in the telecommunications industry in the Republic of Cyprus. For the purposes of this study, a literature review was undertaken which was divided in three parts. The first part includes aspects related to Supply Chain Management, the second part includes the best practice of Human Resource Ma...

The colon is inhabited by a dense population of microorganisms, the so-called "gut microbiota," able to ferment carbohydrates and proteins that escape absorption in the small intestine during digestion. This microbiota produces a wide range of metabolites, including short chain fatty acids (SCFA). These compounds are absorbed in the large bowel and are defined as 1-6 carbon volatile fatty acids which can present straight or branched-chain conformation. Their production is influenced by the pa...

The Internet has changed the way business is conducted in many ways. For example, in the field of procurement, the possibility to directly interact with a trading partner has given rise to new mechanisms in the supply chain management. One such interactive dynamic procurement, which lets both buyer and seller software agents bid by potential buyer agents instead of static procurement by vendors. Dynamic procurement decision could provide the buying and selling channel to buyer, to avoid occurring condition that seller could not deliver on the contract promise. Using NYOP(Name Your Own Price) to be the core of dynamic procurement negotiation algorithm sets up multi-agent dynamic supply chain system, to present the DSINs(Dynamic Supply Chain Information Networks) by JADE, and to present the dynamic supply chain logistic simulation by eM-Plant. Finally, evaluating supply chain performance with supply chain performance metrics (such as bullwhip, fill rate), to be the reference of enterprise making deciding in the...

The production of food products requires a proper control system to guarantee the quality of the products at the end of the distribution chain. A HACCP (Hazard Analysis of Critical Control Points) system provides a scheme for proper handling in a cold chain. Two examples are described: a cold chain for chilled meat and a cold chain for frozen products. For each step in the chains the critical control points are described. The indicated parameters had to be monitored and controlled to achieve good end products. [Dutch] Om bederfelijke producten veilig bij de gebruiker te brengen is een keten van handelingen nodig: de koudeketen. De parameters van de toegepas-te processtappen dienen beheerst te worden. Hiervoor kan men het HACCP ((Hazard Analysis of Critical Control Points) systeem gebruiken. Twee voorbeelden worden gegeven: een koelketen voor vers vlees en een vriesketen. Voor beide ketens wordt voor een aantal processtappen aangegeven welke grootheden kritisch zijn en dus beheerst moeten worden om tot een goed resultaat te komen.

The incorporation of Al and increased curing temperature promotes the crystallization and cross-linking of calcium (alumino)silicate hydrate (C-(A-)S-H), which is the primary binding phase in most contemporary concrete materials. However, the influence of Al-induced structural changes on the mechanical properties at atomistic scale is not well understood. Herein, synchrotron radiation-based high-pressure X-ray diffraction is used to quantify the influence of dreierketten chain cross-linking on the anisotropic mechanical behavior of C-(A-)S-H. We show that the ab-planar stiffness is independent of dreierketten chain defects, e.g. vacancies in bridging tetrahedra sites and Al for Si substitution. The c-axis of non-cross-linked C-(A-)S-H is more deformable due to the softer interlayer opening but stiffens with decreased spacing and/or increased zeolitic water and Ca2+ of the interlayer. Dreierketten chain cross-links act as ‘columns’ to resist compression, thus increasing the bulk modulus of C-(A-)S-H. We provide the first experimental evidence on the influence of the Al-induced atomistic configurational change on the mechanical properties of C-(A-)S-H. Our work advances the fundamental knowledge of C-(A-)S-H on the lowest level of its hierarchical structure, and thus can impact the way that innovative C-(A-)S-H-based cementitious materials are developed using a ‘bottom-up’ approach. PMID:28281635

Understanding how biogeochemical cycles relate to the structure of ecological communities is a central research question in ecology. Here we approach this problem by focusing on body size, which is an easily measured species trait that has a pervasive influence on multiple aspects of community structure and ecosystem functioning. We test the predictions of a model derived from metabolic theory using data on ecosystem metabolism and community size structure. These data were collected as part of an aquatic mesocosm experiment that was designed to simulate future environmental warming. Our analyses demonstrate significant linkages between community size structure and ecosystem functioning, and the effects of warming on these links. Specifically, we show that carbon fluxes were significantly influenced by seasonal variation in temperature, and yielded activation energies remarkably similar to those predicted based on the temperature dependencies of individual-level photosynthesis and respiration. We also show that community size structure significantly influenced fluxes of ecosystem respiration and gross primary production, particularly at the annual time-scale. Assessing size structure and the factors that control it, both empirically and theoretically, therefore promises to aid in understanding links between individual organisms and biogeochemical cycles, and in predicting the responses of key ecosystem functions to future environmental change.

Full Text Available This paper presents a new approach for designing a Fuzzy Logic Controller "FLC"for a dynamically multivariable nonlinear coupling system. The conventional controller with constant gains for different operating points may not be sufficient to guarantee satisfactory performance for Robot manipulator. The Fuzzy Logic Controller utilizes the error and the change of error as fuzzy linguistic inputs to regulate the system performance. The proposed controller have been developed to simulate the dynamic behavior of A Two-LinkFunctional Manipulator. The new controller uses only the available information of the inputoutput for controlling the position and velocity of the robot axes of the motion of the end effectors

This paper compares alternative ways of measuring participation of a country in Global Value Chains (GVCs) and estimates distribution of gains among countries in terms of countries’ shares in total value-added created by trade under GVCs. Using the OECD-WTO database on Trade in Value Added, this paper shows that 67% of total global value created under global value chains, accrue to OECD countries while share of NICs and BRICs countries is 25%. Only 8% of total value added is shared among all ...

Poly(ethylene glycol) or PEG is a hydrophilic polymer that covalently linked to therapeutical proteins may significantly increase their pharmacological properties. Despite the extensive production of PEG-conjugated proteins the effects of the polymer on the protein structure and dynamics is poorly understood, making the production of active biomaterials a largely unpredictable process. The present investigation examines the effects of 5 k and 20 k PEG on the internal flexibility of Ribonuclease T1, the mutant C112S of azurin from Pseudomonas aeruginosa, alcohol dehydrogenase and alkaline phosphatase, native and Zn-depleted. These systems encompass structural domains that range from rather superficial, flexible sites to deeply buried, rigid cores. The approach is based on three sensitive parameters related to the phosphorescence emission of internal Trp residues, namely, the intrinsic room-temperature phosphorescence lifetime (tau(0)) that reports on the local flexibility of the protein matrix around the chromophore and the bimolecular rate constant (k(q)) for the quenching of phosphorescence by O(2) and by acrylamide in solution, which are related to the diffusion of these solutes through the protein fold. The results obtained by these three independent, intrinsic probes of protein structure-dynamics concur that mono-PEGylation does not detectably perturb the conformation and dynamics of the protein native fold, over a wide temperature range. The implication is that protein motions are essentially not coupled to the polymer and that adverse effects of chemical modification on biological function are presumably owed to steric hindrance by PEG units blocking the access to sites critical for molecular recognition.

Full Text Available In the title compound poly[aquabis(μ-nitrato-κ4O,O′:O,O′′tetrakis(nitrato-κ2O,O′{μ4-tetraethyl [(ethane-1,2-diylbis(azanediylbis(2-oxoethane-2,1-diyl]diphosphonate-κ2O,O′}disamarium(III], [Sm2(NO36(C14H30N2O8P2(H2O]n, a 12-coordinate SmIII and a nine-coordinate SmIII cation are alternately linked via shared bis-bidentate nitrate anions into a corrugated chain extending parallel to the a axis. The nine-coordinate SmIII atom of this chain is also chelated by a bidentate, yet flexible, carbamoylmethylphoshine oxide (CMPO ligand and bears one water molecule. This water molecule is hydrogen bonded to nitrate groups bonded to the 12-coordinate SmIII cation. The CMPO ligand, which lies about an inversion center, links neighboring chains along the c axis, forming sheets parallel to the ac plane. Hydrogen bonds between the amide NH group and metal-bound nitrate anions are also present in these sheets. The sheets are packed along the b axis through only van der Waals interactions.

The Tax protein of human T-cell leukemia virus type 1 (HTLV-1) is crucial for the development of adult T-cell leukemia (ATL), a highly malignant CD4+ T cell neoplasm. Among the multiple aberrant Tax-induced effects on cellular processes, persistent activation of transcription factor NF-κB, which is activated only transiently upon physiological stimulation, is essential for leukemogenesis. We and others have shown that Tax induces activation of the IκB kinase (IKK) complex, which is a critical step in NF-κB activation, by generating Lys63-linked polyubiquitin chains. However, the molecular mechanism underlying Tax-induced IKK activation is controversial and not fully understood. Here, we demonstrate that Tax recruits linear (Met1-linked) ubiquitin chain assembly complex (LUBAC) to the IKK complex and that Tax fails to induce IKK activation in cells that lack LUBAC activity. Mass spectrometric analyses revealed that both Lys63-linked and Met1-linked polyubiquitin chains are associated with the IKK complex. Furthermore, treatment of the IKK-associated polyubiquitin chains with Met1-linked-chain-specific deubiquitinase (OTULIN) resulted in the reduction of high molecular weight polyubiquitin chains and the generation of short Lys63-linked ubiquitin chains, indicating that Tax can induce the generation of Lys63- and Met1-linked hybrid polyubiquitin chains. We also demonstrate that Tax induces formation of the active macromolecular IKK complex and that the blocking of Tax-induced polyubiquitin chain synthesis inhibited formation of the macromolecular complex. Taken together, these results lead us to propose a novel model in which the hybrid-chain-dependent oligomerization of the IKK complex triggered by Tax leads to trans-autophosphorylation-mediated IKK activation. PMID:28103322

The Tax protein of human T-cell leukemia virus type 1 (HTLV-1) is crucial for the development of adult T-cell leukemia (ATL), a highly malignant CD4+ T cell neoplasm. Among the multiple aberrant Tax-induced effects on cellular processes, persistent activation of transcription factor NF-κB, which is activated only transiently upon physiological stimulation, is essential for leukemogenesis. We and others have shown that Tax induces activation of the IκB kinase (IKK) complex, which is a critical step in NF-κB activation, by generating Lys63-linked polyubiquitin chains. However, the molecular mechanism underlying Tax-induced IKK activation is controversial and not fully understood. Here, we demonstrate that Tax recruits linear (Met1-linked) ubiquitin chain assembly complex (LUBAC) to the IKK complex and that Tax fails to induce IKK activation in cells that lack LUBAC activity. Mass spectrometric analyses revealed that both Lys63-linked and Met1-linked polyubiquitin chains are associated with the IKK complex. Furthermore, treatment of the IKK-associated polyubiquitin chains with Met1-linked-chain-specific deubiquitinase (OTULIN) resulted in the reduction of high molecular weight polyubiquitin chains and the generation of short Lys63-linked ubiquitin chains, indicating that Tax can induce the generation of Lys63- and Met1-linked hybrid polyubiquitin chains. We also demonstrate that Tax induces formation of the active macromolecular IKK complex and that the blocking of Tax-induced polyubiquitin chain synthesis inhibited formation of the macromolecular complex. Taken together, these results lead us to propose a novel model in which the hybrid-chain-dependent oligomerization of the IKK complex triggered by Tax leads to trans-autophosphorylation-mediated IKK activation.

The paper discusses how designers, conducting design projects in specific organization's, can assure that the design of IT is appropriately linked to the organizations overall business strategy. A case study is presented in the form of a design project in a small public organization. Functional...... analysis was used as a means to clarify how a specific needed information system could support the organization's new business strategy. Using functional analysis in the design project had a powerful effect: it seriously challenged the organization's business strategy and revealed that the system...... to the relation between an organization's IT-projects and its business strategy and by suggesting that it is the responsibility of the designers, conducting design projects, to assure that this task is taken proper care of. Practical guidelines for this purpose are given....

Short pristine multi-walled carbon nanotubes (MWNTs) were functionalized with a series of long-chain (including polymeric) aliphatic amines, namely octadecylamine (ODA), 1,8-diaminooctane (DO), polyethylene glycol diamine (PEGDA) and polyethylenimine (PEI), via two "green" approaches: (1) gas-phase functionalization (for volatile ODA and DO) and (2) direct heating in the melt (for polymeric PEGDA and PEI). Both of them consist in one-step reaction between MWNTs and amine without the use of organic solvents. The nanostructures obtained were characterized by using infrared spectroscopy, thermogravimetric analysis, scanning electron microscopy, atomic force microscopy, and transmission electron microscopy. It was observed that both solvent-free methods were efficient in the nanotube functionalization, and the nanostructures of variable solubility and morphology were obtained depending on the amines attached. ODA, PEGDA and PEI-functionalized MWNTs were found to be soluble in propanol, meanwhile the MWNTs-PEGDA and MWNTs-PEI were soluble in water as well. The attachment of 1,8-diaminooctane onto MWNTs resulted in cross-linked stable nanostructure.

Full Text Available The supply chain is a network of suppliers and customers offering their products or services to the end consumers. The research aimed at recognizing the elements of the supply chain of pork in the area of supply, processing and distribution. The information was primarily sourced by the data storage statistics and chosen meat companies listed among the 2000 largest industries in Poland. The domestic supply chain of pork is characterized by a considerable fragmentation of production, processing and distribution. A signifi cant number of entities and the absence of capital tie-ups between the breeders and the meat industry does not foster durable integration. In order to maintain the profi tability of production, the meat establishments diversify their activities. Entities with large production volume more often cooperate with commercial networks, whereas in case of the smaller ones, these are their own distribution networks that prevail. The leaders in the industry are characterized by a wide range of goods, large-scale production, specialization and a closer integration in the supply chain.

The macroporous anion exchangers with long-chained cross-linking agents were investigated for the tungsten recovery from salt solutions. The physical-chemical characteristics of these sorbents were studied by means of sorption-desorption experiment aswell as electron and IR-spectroscopy. The anion exchangers on the basis of macroporous copolymers of methylacrylate and divinyl-ester of diethyleneglycol or tetravinyl-ester of pentaerythritol possess the exchange capacity to tungsten 2--5 times greater than the porous anion exchangers on the basis of styrene and divinylbenzene, therefore they can be used for selective tungsten recovery from comulex salt solutions.

This is the first report to have identified an O-linked repetitive glycan in bacterial flagellin, a structural protein of the flagellum. Studies by sugar analysis, Smith degradation, (1)H and (13)C NMR spectroscopy, and mass spectrometry showed that the glycan chains of the polar flagellum flagellin of the plant-growth-promoting rhizobacterium Azospirillum brasilense Sp7 are represented by a polysaccharide with a molecular mass of 7.7 kDa, which has a branched tetrasaccharide repeating unit of the following structure:

We studied the properties of bilayers formed by ether-and ester-containing phospholipids, whose hydrocarbon chains can be either linear or branched, using sn-1,2 dipalmitoyl, dihexadecyl, diphytanoyl, and diphytanyl phosphatidylcholines (DPPC, DHPC, DPhoPC, and DPhPC, respectively) either pure or in binary mixtures. Differential scanning calorimetry and confocal fluorescence microscopy of giant unilamellar vesicles concurred in showing that equimolar mixtures of linear and branched lipids gave rise to gel/fluid phase coexistence at room temperature. Mixtures containing DHPC evolved in time (0.5 h) from initial reticulated domains to extended solid ones when an equilibrium was achieved. The nanomechanical properties of supported planar bilayers formed by each of the four lipids studied by atomic force microscopy revealed average breakdown forces Fb decreasing in the order DHPC ≥ DPPC > DPhoPC > DPhPC. Moreover, except for DPPC, two different Fb values were found for each lipid. Atomic force microscopy imaging of DHPC was peculiar in showing two coexisting phases of different heights, probably corresponding to an interdigitated gel phase that gradually transformed, over a period of 0.5 h, into a regular tilted gel phase. Permeability to nonelectrolytes showed that linear-chain phospholipids allowed a higher rate of solute + water diffusion than branched-chain phospholipids, yet the former supported a smaller extent of swelling of the corresponding vesicles. Ether or ester bonds appeared to have only a minor effect on permeability.

A growing research stream has expanded the level of analysis beyond single buyer-supplier relations to the network, including supplier-supplier relations. These supplier-supplier relations may constitute a missing link between the traditional analysis of the dyadic and the network level of analysis

A growing research stream has expanded the level of analysis beyond single buyer-supplier relations to the network, including supplier-supplier relations. These supplier-supplier relations may constitute a missing link between the traditional analysis of the dyadic and the network level of analysis

Functional connectivity network (FCN) is an effective tool in psychiatry disorders classification, and represents cross-correlation of the regional blood oxygenation level dependent signal. However, FCN is often incomplete for suffering from missing and spurious edges. To accurate classify psychiatry disorders and health control with the incomplete FCN, we first `repair' the FCN with link prediction, and then exact the clustering coefficients as features to build a weak classifier for every FCN. Finally, we apply a boosting algorithm to combine these weak classifiers for improving classification accuracy. Our method tested by three datasets of psychiatry disorder, including Alzheimer's Disease, Schizophrenia and Attention Deficit Hyperactivity Disorder. The experimental results show our method not only significantly improves the classification accuracy, but also efficiently reconstructs the incomplete FCN.

Biological soil crusts (BSCs) are an association of different microorganisms and soil particles in the top millimeters of the soil. They are formed by algae, cyanobacteria, microfungi, bacteria, bryophytes and lichens in various compositions. Our aim was to determine and compare the biodiversity of all occurring organisms in biogeographically different habitats, ranging from polar (both Arctic and Antarctic), subpolar (Scandinavia), temperate (Germany) to dry regions (Chile). The combination of microscopy and molecular techniques (next-generation sequencing) revealed highly diverse crust communities, whose composition clustered by region and correlates with habitat characteristics such as water content. The BSC biodiversity was then linked to the ecological function of the crusts. The functional role of the BSCs in the biogeochemical cycles of carbon, nitrogen and phosphorous is evaluated using an array of state of the art soil chemistry methods including Py-FIMS (pyrolysis field ionization mass spectrometry) and XANES (x-ray absorbance near edge structure). Total P as well as P fractions were quantified in all BSCs, adjacent soil underneath and comparable nearby soil of BSC-free areas revealing a remarkable accumulation of total phosphorous and a distinct pattern of P fractions in the crust. Further, we observed an indication of a different P-speciation composition in the crust compared with BSC-free soil. The data allow answering the question whether BSCs act as sink or source for these compounds, and how biodiversity controls the biogeochemical function of BSCs.

Full Text Available This paper presents development in the bioinformatics services industry value chain, based on cloud computing paradigm. As genome sequencing costs per Megabase exponentially drop, industry needs to adopt. Paper has two parts: theoretical analysis and practical example of Seven Bridges Genomics Company. We are focused on explaining organizational, business and financial aspects of new business model in bioinformatics services, rather than technical side of the problem. In the light of that we present twofold business model fit for core bioinformatics research and Information and Communication Technologie (ICT support in the new environment, with higher level of capital utilization and better resistance to business risks.

Full Text Available The colon is inhabited by a dense population of microorganisms, the so-called gut microbiota, able to ferment carbohydrates and proteins that escape absorption in the small intestine during digestion. This microbiota produces a wide range of metabolites, including short chain fatty acids (SCFA. These compounds are absorbed in the large bowel and are defined as 1-6 carbon volatile fatty acids which can present straight or branched-chain conformation. Their production is influenced by the pattern of food intake and diet-mediated changes in the gut microbiota. SCFA have distinct physiological effects: they contribute to shaping the gut environment, influence the physiology of the colon, they can be used as energy sources by host cells and the intestinal microbiota and they also participate in different host-signalling mechanisms. We summarize the current knowledge about the production of SCFA, including bacterial cross-feedings interactions, and the biological properties of these metabolites with impact on the human health

The improvement of living standards increase concentration of people, infrastructure and goods in environmentally privileged but often hazardous places. Communities in mountainous regions are exposed to several hazardous processes, including snow avalanches, storms, floods, landslides, rockfalls and debris flows. The disastrous events over last decades clearly show that adequate security in mountain areas remains limited despite preventive measures. Thus, advanced development and improvement of mountain risk issues is of importance. Within the "Mountain Risks" project a lot of research attention is concentrated on the Ubaye Valley, in French Alps. Researchers working in this region cover the whole chain of the 'living with risk' process: from improving predictions to decision-making, through understanding of natural processes, quantitative risk assessment and socio-economic aspects. As "insiders", we have observed interesting differences between representatives from different sciences, for instance in the terminology, the priorities defined, the value granted to each others' work. It has been challenging to adapt our way of thinking and acting in order to build up useful and valuable results than can be of use for every interested part of the chain. Herein we want to share the lessons learnt during this project. How does "multidisciplinarity" works on the ground? What are the gaps between the different sciences involved? How can we bridge those gaps?

We model an epidemic with a class of nonhomogeneous Markov chains on the supercritical percolation network on Zd.The large deviations law for the Markov chain is given.Explicit expression of the rate function for large deviation is obtained.

The bispyrazolines 4a(a'-f') and 4b(a'-f') built around the aliphatic chains of varying lengths have been prepared by refluxing bischalcones 3a(a'-f') and 3b(a'-f') with phenyl hydrazine in alcoholic medium. The reactions of chalcones 2a and 2b with suitable 1,ω-dibromoalkanes in the presence of anhydrous K2CO3/dry acetone and Bu4N+I- (PTC) provided 3a(a'-f') and 3b(a'-f'), respectively. The antibacterial and antifungal activities of the synthesized compounds were evaluated against five bacterial and four fungal strains. The compounds 3ba', 3bc', 3bd', 3be', 3af', 4aa' and 4ba' showed better MIC (μg/mL) against the tested microorganisms.

With earth-science datasets increasingly being published to enable re-use in projects disassociated from the original data acquisition or generation, there is an urgent need for associated metadata to be connected, in order to guide their application. In particular, provenance traces should support the evaluation of data quality and reliability. However, while standards for describing provenance are emerging (e.g. PROV-O), these do not include the necessary statistical descriptors and confidence assessments. UncertML has a mature conceptual model that may be used to record uncertainty metadata. However, by itself UncertML does not support the representation of uncertainty of multi-part datasets, and provides no direct way of associating the uncertainty information - metadata in relation to a dataset - with dataset objects.We present a method to address both these issues by combining UncertML with PROV-O, and delivering resulting uncertainty-enriched provenance traces through the Linked Data API. UncertProv extends the PROV-O provenance ontology with an RDF formulation of the UncertML conceptual model elements, adds further elements to support uncertainty representation without a conceptual model and the integration of UncertML through links to documents. The Linked ID API provides a systematic way of navigating from dataset objects to their UncertProv metadata and back again. The Linked Data API's 'views' capability enables access to UncertML and non-UncertML uncertainty metadata representations for a dataset. With this approach, it is possible to access and navigate the uncertainty metadata associated with a published dataset using standard semantic web tools, such as SPARQL queries. Where the uncertainty data follows the UncertML model it can be automatically interpreted and may also support automatic uncertainty propagation . Repositories wishing to enable uncertainty propagation for all datasets must ensure that all elements that are associated with uncertainty

We report theoretical studies on the plasmon resonances in linear Au atomic chains by using ab initio timedependent density functional theory. The dipole responses are investigated each as a function of chain length. They converge into a single resonance in the longitudinal mode but split into two transverse modes. As the chain length increases,the longitudinal plasmon mode is redshifted in energy while the transverse modes shift in the opposite direction (blueshifts). In addition,the energy gap between the two transverse modes reduces with chain length increasing. We find that there are unique characteristics,different from those of other metallic chains. These characteristics are crucial to atomic-scale engineering of single-molecule sensing,optical spectroscopy,and so on.

Electronic properties and STM topographical images of X (=F, H, O) functionalized silicene and germanene have been investigated by introducing various kind of vacancy clusters and chain patterns in monolayers within density functional theory (DFT) framework. The relative ease of formation of vacancy clusters and chain patterns is found to be energetically most favorable in hydrogenated silicene and germanene. F- and H-functionalized silicene and germanene are direct bandgap semiconducting with bandgap ranging between 0.1-1.9 eV, while O-functionalized monolayers are metallic in nature. By introducing various vacancy clusters and chain patterns in both silicene and germanene, the electronic and magnetic properties get modified in significant manner e.g. F- and H-functionalized silicene and germanene with hexagonal and rectangle vacancy clusters are non-magnetic semiconductors with modified bandgap values while pentagonal and triangle vacancy clusters induce metallicity and magnetic character in monolayers; hexagonal vacancy chain patterns induce direct-to-indirect gap transition while zigzag vacancy chain patterns retain direct bandgap nature of monolayers. Calculated STM topographical images show distinctly different characteristics for various type of vacancy clusters and chain patterns which may be used as electronic fingerprints to identify various vacancy patterns in silicene and germanene created during the process of functionalization.

We evaluated functional communication training (FCT) combined with a chained schedule of reinforcement procedure for the treatment of challenging behavior exhibited by two individuals diagnosed with Asperger syndrome and autism. Following functional analyses that suggested that challenging behavior served multiple functions for both participants,…

Full Text Available For many cities throughout the world, climate change not only presents challenges in the form of new risks and expenses, but also opportunities to connect work around climate change to other development and environmental initiatives. This study presents the City of Toledo in the heart of America’s Rust Belt as a case study of the policy process that gives rise to proactive action on climate change. Using thick description, we trace Toledo’s adaptation policy process through the lens of Kingdon’s “multiple streams” model to identify factors that have shaped the emergence of climate adaptation work around water management in Toledo. Through doing so, we give particular attention to the knowledge resources that those in the City have relied on, especially its boundary chain connection with two supporting boundary organizations: GLAA-C and GLISA. Policy entrepreneurs pushing for climate adaptation around water policy in Toledo emerged around two separate pieces of the policy process. The first entrepreneur was involved with raising general awareness about sustainability and climate change in the City’s problem stream, and the other was specifically involved with integrating climate change information into a particular aspect of the City’s policy stream, water management. While these relationships were important for mainstreaming climate change adaptation into efforts to address existing challenges, they were also representative of the City’s ability to cultivate broader partnerships around climate adaptation. Toledo’s polycentric climate change network ultimately helped the City sustain its adaptation work as it weathered its own period of internal transition.

Advanced glycation end products (AGEs) are a diverse group of compounds produced when reducing sugars react with proteins or other compounds to form glycosylated molecules. AGEs may form endogenously, and glycation of molecules may negatively affect their function. AGEs may also be consumed in food form with dietary AGEs reported to be particularly high in foods treated with high heat: baked, broiled, grilled, and fried foods. Whether dietary AGEs are absorbed in significant quantities and whether they are harmful if absorbed is a question under current debate. The American Diabetes Association makes no recommendation regarding avoidance of these foods, but many researchers are concerned that they may be pro-inflammatory and way worsen cardiac function, kidney function, diabetes and its complications and may even contribute to obesity.

A linked perceptual class consists of two distinct perceptual classes, A' and B', the members of which have become related to each other. For example, a linked perceptual class might be composed of many pictures of a woman (one perceptual class) and the sounds of that woman's voice (the other perceptual class). In this case, any sound of the…

Spatial generalized linear mixed models (SGLMMs) are popular models for spatial data with a non-Gaussian response. Binomial SGLMMs with logit or probit linkfunctions are often used to model spatially dependent binomial random variables. It is known that for independent binomial data, the robit regression model provides a more robust (against extreme observations) alternative to the more popular logistic and probit models. In this article, we introduce a Bayesian spatial robit model for spatially dependent binomial data. Since constructing a meaningful prior on the linkfunction parameter as well as the spatial correlation parameters in SGLMMs is difficult, we propose an empirical Bayes (EB) approach for the estimation of these parameters as well as for the prediction of the random effects. The EB methodology is implemented by efficient importance sampling methods based on Markov chain Monte Carlo (MCMC) algorithms. Our simulation study shows that the robit model is robust against model misspecification, and our EB method results in estimates with less bias than full Bayesian (FB) analysis. The methodology is applied to a Celastrus Orbiculatus data, and a Rhizoctonia root data. For the former, which is known to contain outlying observations, the robit model is shown to do better for predicting the spatial distribution of an invasive species. For the latter, our approach is doing as well as the classical models for predicting the disease severity for a root disease, as the probit link is shown to be appropriate. Though this article is written for Binomial SGLMMs for brevity, the EB methodology is more general and can be applied to other types of SGLMMs. In the accompanying R package geoBayes, implementations for other SGLMMs such as Poisson and Gamma SGLMMs are provided.

of siloxane copolymers[1] (via the tris(pentafluorophenyl)borane catalysed Piers-Rubinsztajn reaction[2]), which allows for the attachment of functional molecules through copper-catalysed azide-alkyne 1,3-dipolar cycloaddition (CuAAC)[3]. The synthesised copolymers allow for a high degree of chemical freedom...

As it is clear that the full packaging life cycle – at least partially – coincides with the product life cycle, both cycles are interwoven. Each has a network of functional requirements, with specific hierarchic propensities. These networks overlap, with prevailing hierarchies playing important

Human severe combined immunodeficiency (SCID), a syndrome of profoundly impaired cellular and humoral immunity, is most commonly caused by mutations in the X-linked gene for interleukin-2 (IL-2) receptor {gamma} chain (IL2RG). For mutational analysis of IL2RG in males with SCID, SSCP screening was followed by DNA sequencing. Of 40 IL2RG mutations found in unrelated SCID patients, 6 were point mutations at the CpG dinucleotide at cDNA 690-691, encoding amino acid R226. This residue lies in the extracellular domain of the protein in a region not previously recognized to be significantly conserved in the cytokine receptor gene family, 11 amino acids upstream from the highly conserved WSXWS motif. Three additional instances of mutation at another CpG dinucleotide at cDNA 879 produced a premature termination signal in the intracellular domain of IL2RG, resulting in loss of the SH2-homologous intracellular domain known to be essential for signaling from the IL-2 receptor complex. Mutations at these two hotspots constitute >20% of the X-linked SCID mutations found by our group and a similar proportion of all reported IL2RG mutations. 41 refs., 5 figs., 1 tab.

Recent research has demonstrated how cross-linking of pectic polysaccharides to obtain gel formation can be promoted by enzymatic catalysis reactions, and provide opportunities for functional upgrading of pectic polysaccharides present in agro-industrial sidestreams. This review highlights...... the mechanisms of formation of functional pectic polysaccharide cross-links, including covalent cross-links (notably phenolic esters and uronyl ester linkages) and non-covalent, ionic cross-links (which involve calcium and borate ester links). The treatise examines how such cross-links can be designed via...

Cytoplasmic dynein transports cargoes for a variety of crucial cellular functions. However, since dynein is essential in most eukaryotic organisms, the in-depth study of the cellular function of dynein via genetic analysis of dynein mutations has not been practical. Here, we identify and characterize 34 different dynein heavy chain mutations using a genetic screen of the ascomycete fungus Neurospora crassa, in which dynein is nonessential. Interestingly, our studies show that these mutations segregate into five different classes based on the in vivo localization of the mutated dynein motors. Furthermore, we have determined that the different classes of dynein mutations alter vesicle trafficking, microtubule organization, and nuclear distribution in distinct ways and require dynactin to different extents. In addition, biochemical analyses of dynein from one mutant strain show a strong correlation between its in vitro biochemical properties and the aberrant intracellular function of that altered dynein. When the mutations were mapped to the published dynein crystal structure, we found that the three-dimensional structural locations of the heavy chain mutations were linked to particular classes of altered dynein functions observed in cells. Together, our data indicate that the five classes of dynein mutations represent the entrapment of dynein at five separate points in the dynein mechanochemical and transport cycles. We have developed N. crassa as a model system where we can dissect the complexities of dynein structure, function, and interaction with other proteins with genetic, biochemical, and cell biological studies. PMID:22649085

Thermal transport across one-dimensional atomic chains is studied using a harmonic nonequilibrium Green’s function formalism in the ballistic phonon transport regime. Introducing a mass impurity in the chain and mass loading in the thermal contacts leads to interference of phonon waves, which can be manipulated by varying the magnitude of the loading. This shows that thermal rectification is tunable in a completely harmonic system.

This paper investigates the problem of how to handling demand disruptions in a one-supplier-one-retailer supply chain, where production cost is a convex function of production quantity andprice-demand relationship is linear. Our results show that, if demand is disrupted, under the new price-demand relationship, all-unit wholesale quantity discount policies combining capacitated linear pricingpolicies can also fully coordinate the supply chain.

This volume presents seven case studies of global value chains alongside two theoretical chapters concerning these chains. The contributors explore a wide range of issues relevant to value chains: the impact of global value chains on local upgrading strategies, the role of governance structures

A visual approach to understanding the chain rule and related derivative formulae, for functions from R to R and from C to C, is presented. This apparently novel approach has been successfully used with several audiences: students first studying calculus, students with some background in linear algebra, students beginning study of functions of a…

A visual approach to understanding the chain rule and related derivative formulae, for functions from R to R and from C to C, is presented. This apparently novel approach has been successfully used with several audiences: students first studying calculus, students with some background in linear algebra, students beginning study of functions of a…

Arbuscular mycorrhizal fungi (AMF) are crucial components of fertile soils, able to provide several ecosystem services for crop production. Current economic, social and legislative contexts should drive the so-called “second green revolution” by better exploiting these beneficial microorganisms. Many challenges still need to be overcome to better understand the mycorrhizal symbiosis, among which (i) the biotrophic nature of AMF, constraining their production, while (ii) phosphate acts as a limiting factor for the optimal mycorrhizal inoculum application and effectiveness. Organism fitness and adaptation to the changing environment can be driven by the modulation of mitochondrial respiratory chain, strongly connected to the phosphorus processing. Nevertheless, the role of the respiratory function in mycorrhiza remains largely unexplored. We hypothesized that the two mitochondrial respiratory chain components, alternative oxidase (AOX) and cytochrome oxidase (COX), are involved in specific mycorrhizal behavior. For this, a complex approach was developed. At the pre-symbiotic phase (axenic conditions), we studied phenotypic responses of Rhizoglomus irregulare spores with two AOX and COX inhibitors [respectively, salicylhydroxamic acid (SHAM) and potassium cyanide (KCN)] and two growth regulators (abscisic acid – ABA and gibberellic acid – Ga3). At the symbiotic phase, we analyzed phenotypic and transcriptomic (genes involved in respiration, transport, and fermentation) responses in Solanum tuberosum/Rhizoglomus irregulare biosystem (glasshouse conditions): we monitored the effects driven by ABA, and explored the modulations induced by SHAM and KCN under five phosphorus concentrations. KCN and SHAM inhibited in vitro spore germination while ABA and Ga3 induced differential spore germination and hyphal patterns. ABA promoted mycorrhizal colonization, strong arbuscule intensity and positive mycorrhizal growth dependency (MGD). In ABA treated plants, R. irregulare

Full Text Available The functional diversity of a community can influence ecosystem functioning and reflects assembly processes. The large number of disparate metrics used to quantify functional diversity reflects the range of attributes underlying this concept, generally summarized as functional richness, functional evenness, and functional divergence. However, in practice, we know very little about which attributes drive which ecosystem functions, due to a lack of field-based tests. Here we test the association between eight leading functional diversity metrics (Rao's Q, FD, FDis, FEve, FDiv, convex hull volume, and species and functional group richness that emphasize different attributes of functional diversity, plus 11 extensions of these existing metrics that incorporate heterogeneous species abundances and trait variation. We assess the relationships among these metrics and compare their performances for predicting three key ecosystem functions (above- and belowground biomass and light capture within a long-term grassland biodiversity experiment. Many metrics were highly correlated, although unique information was captured in FEve, FDiv, and dendrogram-based measures (FD that were adjusted by abundance. FD adjusted by abundance outperformed all other metrics in predicting both above- and belowground biomass, although several others also performed well (e.g. Rao's Q, FDis, FDiv. More generally, trait-based richness metrics and hybrid metrics incorporating multiple diversity attributes outperformed evenness metrics and single-attribute metrics, results that were not changed when combinations of metrics were explored. For light capture, species richness alone was the best predictor, suggesting that traits for canopy architecture would be necessary to improve predictions. Our study provides a comprehensive test linking different attributes of functional diversity with ecosystem function for a grassland system.

The functional diversity of a community can influence ecosystem functioning and reflects assembly processes. The large number of disparate metrics used to quantify functional diversity reflects the range of attributes underlying this concept, generally summarized as functional richness, functional evenness, and functional divergence. However, in practice, we know very little about which attributes drive which ecosystem functions, due to a lack of field-based tests. Here we test the association between eight leading functional diversity metrics (Rao's Q, FD, FDis, FEve, FDiv, convex hull volume, and species and functional group richness) that emphasize different attributes of functional diversity, plus 11 extensions of these existing metrics that incorporate heterogeneous species abundances and trait variation. We assess the relationships among these metrics and compare their performances for predicting three key ecosystem functions (above- and belowground biomass and light capture) within a long-term grassland biodiversity experiment. Many metrics were highly correlated, although unique information was captured in FEve, FDiv, and dendrogram-based measures (FD) that were adjusted by abundance. FD adjusted by abundance outperformed all other metrics in predicting both above- and belowground biomass, although several others also performed well (e.g. Rao's Q, FDis, FDiv). More generally, trait-based richness metrics and hybrid metrics incorporating multiple diversity attributes outperformed evenness metrics and single-attribute metrics, results that were not changed when combinations of metrics were explored. For light capture, species richness alone was the best predictor, suggesting that traits for canopy architecture would be necessary to improve predictions. Our study provides a comprehensive test linking different attributes of functional diversity with ecosystem function for a grassland system.

Full Text Available The current trends of product customization and repair of high value parts with individual defects demand automation and a high degree of flexibility of the involved manufacturing process chains. To determine the corresponding requirements this paper gives an overview of manufacturing process chains by distinguishing between horizontal and vertical process chains. The established way of modeling and programming processes with CAx systems and existing approaches is shown. Furthermore, the different types of possible adaptions of a manufacturing process chain are shown and considered as a cascaded control loop. Following this it is discussed which key requirements of repair process chains are unresolved by existing approaches. To overcome the deficits this paper introduces repair features which comprise the idea of geometric features and defines analytical auxiliary geometries based on the measurement input data. This meets challenges normally caused by working directly on reconstructed geometries in the form of triangulated surfaces which are prone to artifacts. Embedded into function blocks, this allows the use of traditional approaches for manufacturing process chains to be applied to adaptive repair process chains.

The single-index model with monotonic linkfunction is investigated. Firstly,it is showed that the linkfunction h(·) can be viewed by a graphic method. That is,the plot with the fitted response y on the horizontal axis and the observed y on the vertical axis can be used to visualize the linkfunction. It is pointed out that this graphic approach is also applicable even when the linkfunction is not monotonic. Note that many existing nonparametric smoothers can also be used to assess h(·). Therefore,the I-spline approximation of the linkfunction via maximizing the covariance function with a penalty function is investigated in the present work.The consistency of the criterion is constructed. A small simulation is carried out to evidence the efficiency of the approach proposed in the paper.

A series of novel polyurethanes containing cross-linked siloxane in the side chain (SPU) were successfully synthesized through a sol-gel process. The SPU was composed of 0%–20% N-(n-butyl)-3-aminopropyltriethoxysilane (HDI-T) modified hexamethylene diisocynate homopolymer. The effects of HDI-T content on both the structure and properties of SPU were investigated by Fourier transform infrared spectroscopy (FT-IR), X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), mechanical properties tests, gel content test, water contact angle measurement and water absorption test. FT-IR, XPS and XRD results confirmed the successful incorporation of HDI-T onto polyurethanes and the formation of Si–O–Si. The surface roughness and the Si content of SPU enhanced with the increase of HDI-T content. Both crystallization and melting temperature shifted to a lower point after the incorporation of HDI-T. The hydrophobicity, tensile strength, Young’s modulus and pencil hardness overall increased with the increasing of HDI-T content, whereas the thermal stability and the elongation at break of SPU slightly decreased. PMID:28772607

The effect of ageing and the relationships between the catalytic properties of enzymes linked to Krebs' cycle, electron transfer chain, glutamate and aminoacid metabolism of cerebral cortex, a functional area very sensitive to both age and ischemia, were studied on mitochondria of adult and aged rats, after complete ischemia of 15 minutes duration. The maximum rate (Vmax) of the following enzyme activities: citrate synthase, malate dehydrogenase, succinate dehydrogenase for Krebs' cycle; NADH-cytochrome c reductase as total (integrated activity of Complex I-III), rotenone sensitive (Complex I) and cytochrome oxidase (Complex IV) for electron transfer chain; glutamate dehydrogenase, glutamate-oxaloacetate-and glutamate-pyruvate transaminases for glutamate metabolism were assayed in non-synaptic, perikaryal mitochondria and in two populations of intra-synaptic mitochondria, i.e., the light and heavy mitochondrial fraction. The results indicate that in normal, steady-state cerebral cortex, the value of the same enzyme activity markedly differs according (a) to the different populations of mitochondria, i.e., non-synaptic or intra-synaptic light and heavy, (b) and respect to ageing. After 15 min of complete ischemia, the enzyme activities of mitochondria located near the nucleus (perikaryal mitochondria) and in synaptic structures (intra-synaptic mitochondria) of the cerebral tissue were substantially modified by ischemia. Non-synaptic mitochondria seem to be more affected by ischemia in adult and particularly in aged animals than the intra-synaptic light and heavy mitochondria. The observed modifications in enzyme activities reflect the metabolic state of the tissue at each specific experimental condition, as shown by comparative evaluation with respect to the content of energy-linked metabolites and substrates. The derangements in enzyme activities due to ischemia is greater in aged than in adult animals and especially the non-synaptic and the intra-synaptic light

Full Text Available Trade credit financing is a useful tool in business today, which can be characterized as the agreement between supply chain members such as permissible delay in payments. In this study, we assume that the items have the property of noninstantaneous deterioration and the demand is a function of downstream credit. Then, an EOQ model for noninstantaneous deterioration is built based on the two-level financing policy. The purpose of this paper is to maximize the total average profit by determine the optimal downstream credit period, the optimal replenishment cycle length, and the optimal ordering quantity per cycle. Useful theorems are proposed to characterize the method of obtaining the optimal solutions. Based on the theorems, an algorithm is designed, and numerical tests and sensitive analysis are provided. Lastly, according to the sensitive analysis, managerial insights are proposed.

functional phenotypes that are different from those observed previously in Kv VSDs. In contrast, and similar to results obtained with Kv channels, individually neutralizing acidic side chains with synthetic derivatives and with natural amino acid substitutions in the INC had little or no effect......Voltage-gated sodium (NaV) channels mediate electrical excitability in animals. Despite strong sequence conservation among the voltage-sensor domains (VSDs) of closely related voltage-gated potassium (KV) and NaV channels, the functional contributions of individual side chains in Nav VSDs remain...... largely enigmatic. To this end, natural and unnatural side chain substitutions were made in the S2 hydrophobic core (HC), the extracellular negative charge cluster (ENC), and the intracellular negative charge cluster (INC) of the four VSDs of the skeletal muscle sodium channel isoform (NaV1...

Selective enrichment is a crucial step before the mass spectrometric analysis of glycoproteins. A new approach using 3-aminopropyltriethoxysilane (APTES)-functionalized mesoporous silica materials (SBA-15) was reported to enrich the glycoproteins. Selective extraction of glycopeptides was achieved through coupling the oxidized glycan chains on the glycopeptides with the amine groups on SBA-15 through a reductive amination reaction, then the captured glycopeptides were detached from the SBA-15 for the following MS analysis using the enzyme PNGase F. Because the mesoporous material has a confinement effect, the efficiency of enrichment and enzymatic deglycosylation was improved dramatically. The coupling time was shortened from 4 hours to 1 hour, and the deglycosylation time was greatly shortened from 6 hours to 3 hours. This approach was successfully applied to profile the N-glycoproteome of human colorectal cancer serum. 84 N-linked glycosylation sites from 56 N-linked glycoproteins were identified from as little as 5 μL serum.

Full Text Available Triblock copolymers of polystyrene (PS and a polyolefin (PO, e.g., PS-block-poly(ethylene-co-1-butene-block-PS (SEBS, are attractive materials for use as thermoplastic elastomers and are produced commercially by a two-step process that involves the costly hydrogenation of PS-block-polybutadiene-block-PS. We herein report a one-pot strategy for attaching PS chains to both ends of PO chains to construct PS-block-PO-block-PS directly from olefin and styrene monomers. Dialkylzinc compound containing styrene moieties ((CH2=CHC6H4CH2CH22Zn was prepared, from which poly(ethylene-co-propylene chains were grown via “coordinative chain transfer polymerization” using the pyridylaminohafnium catalyst to afford di-end functional PO chainsfunctionalized with styrene and Zn moieties. Subsequently, PS chains were attached at both ends of the PO chains by introduction of styrene monomers in addition to the anionic initiator Me3SiCH2Li·(pmdeta (pmdeta = pentamethyldiethylenetriamine. We found that the fraction of the extracted PS homopolymer was low (~20% and that molecular weights were evidently increased after the styrene polymerization (ΔMn = 27–54 kDa. Transmission electron microscopy showed spherical and wormlike PS domains measuring several tens of nm segregated within the PO matrix. Optimal tensile properties were observed for the sample containing a propylene mole fraction of 0.25 and a styrene content of 33%. Finally, in the cyclic tensile test, the prepared copolymers exhibited thermoplastic elastomeric properties with no breakage up over 10 cycles, which is comparable to the behavior of commercial-grade SEBS.

Like ubiquitin, the small ubiquitin-related modifier (SUMO) proteins can form oligomeric "chains," but the biological functions of these superstructures are not well understood. Here, we created mutant yeast strains unable to synthesize SUMO chains (smt3(allR)) and subjected them to high-content microscopic screening, synthetic genetic array (SGA) analysis, and high-density transcript profiling to perform the first global analysis of SUMO chainfunction. This comprehensive assessment identified 144 proteins with altered localization or intensity in smt3(allR) cells, 149 synthetic genetic interactions, and 225 mRNA transcripts (primarily consisting of stress- and nutrient-response genes) that displayed a >1.5-fold increase in expression levels. This information-rich resource strongly implicates SUMO chains in the regulation of chromatin. Indeed, using several different approaches, we demonstrate that SUMO chains are required for the maintenance of normal higher-order chromatin structure and transcriptional repression of environmental stress response genes in budding yeast.

The {sup 1}H , {sup 13}C and {sup 15}N NMR spectroscopic data for 1,4-dihydropyridine endowed with long alkyl and functionalizedchain on C-3 and C-5, have been fully assigned by combination of one- and two dimensional experiments (DEPT, HMBC, HMQC, COSY, nOe). (author)

The aim of this study was to improve production level of llama heavy chain antibody fragments (V (HH)) in Saccharomyces cerevisiae while retaining functional characteristics. For this purpose, the DNA shuffling technique was used on llama V (HH) fragments specific for the azo-dye reactive red-6. In

Full Text Available In species from three widely divergent phyla (Arthropoda, Mollusca and Chordata tyrosine derivatives (norepinephrine or octopamine mediate a response to acute stress. Part of this response is a change in immune function that results in a decrease in resistance to pathogens. This decrease in disease resistance appears maladaptive. However, if the connections between norepinephrine/octopamine and immune function were maladaptive, they should have been selected against. None of the four commonly proposed adaptive explanations for acute stress-induced changes in immune function fit the available data for species from all three phyla. However, this result is probably due to the lack of information about acute stress-induced immunosuppression in invertebrates and a lack of ecologically valid studies in vertebrates. Understanding why immune function and disease resistance changes during acute stress will require greater comparative study.

After the establishment of technologies for high-throughput DNA sequencing (genomics), gene expression analysis (transcriptomics), and protein analysis (proteomics), the remaining functional genomics challenge is that of metabolomics. Metabolomics is the term coined for essentially comprehensive, no

The amino acid sequence of the alpha- and beta-chains of haemoglobin (Hb) from the loggerhead sea turtle (Caretta caretta) has been determined. Comparison with that of human Hb shows differences in several residues involved in both alpha 1 beta 1 and alpha 1 beta 2 packing contacts. On the whole, in spite of the mutations, the essential characteristics of both interfaces seem to be maintained. The functional properties of the sea turtle Hb have been investigated at different temperatures and as a function of proton, chloride and organic phosphate concentrations. In addition to overall similarities shared with most of the vertebrate Hbs previously described, this molecule shows significant differences which could be related to the life behaviour of the turtle. In fact, while the shape of the Bohr-effect curve is well adapted for gas exchange during prolonged dives, the very small enthalpy change for O2 binding ensures that O2 delivery becomes essentially insensitive to the temperature changes of the environment. Moreover, and similarly to the case of emperor penguin Hb, the small alkaline Bohr effect appears to be only choride-linked, since the pH dependence of the O2 affinity is abolished in the absence of this ion. These functional characteristics are discussed on the basis of the primary structure of alpha- and beta-chains.

Naji, Raid Kamel [Department of Mathematics, College of Science, University of Baghdad (Iraq)]. E-mail: rknaji@yahoo.com; Balasim, Alla Tariq [Department of Mathematics, College of Science, University of Baghdad (Iraq)]. E-mail: alkhazrejy@yahoo.com

2007-06-15

A three species food chain model with Beddington-DeAngelis functional response is investigated. The local stability analysis is carried out and global behavior is simulated numerically for a biologically feasible choice of parameters. The persistence conditions of a food chain model are established. The bifurcation diagrams are obtained for different parameters of the model after intensive numerical simulations. The results of simulations show that the model could exhibit chaotic dynamics for realistic and biologically feasible parametric values. Finally, the effect of immigration within prey species is investigated. It is observed that adding small amount of constant immigration to prey species stabilize the system.

Mouse monoclonal antibodies (mAbs) were produced against an Indian isolate of egg drop syndrome (EDS) virus and characterized. Four hybridoma clones were secreting mAbs that bound to a 100 kDa protein, presumably the hexon protein. These mAbs were found to cross-react with two other Indian isolates of EDS virus and to the reference UK 127 strain. Three of these mAbs were mapped to the same epitope compared with the other mAb (F8), which bound to a different epitope. An antigen-capture enzyme-linked immunosorbent assay (AC-ELISA) was developed using the F8 mAbs as capture antibody and polyclonal chicken serum against EDS virus as detection antibody. A polymerase chain reaction (PCR) was used to detect the EDS viral genome. Following experimental infection of oestrogen-treated chickens with EDS virus, cloacal swabs, oviduct, uterus and spleen were collected at different days post-infection and used in both AC-ELISA and PCR, directly and after a single passage in embryonated duck eggs. The sensitivity and specificity of antigen detection by AC-ELISA or PCR was 95% and 98%, respectively. For diagnosis of EDS viral infections, PCR is recommended due to its ease and the lack of requirement of prepared reagents such as mAbs or conjugates. We recommend that PCR be performed directly on boiled tissue homogenates. Any negative samples may be passaged in embryonated duck eggs and the allantoic fluids tested by PCR before a conclusive negative diagnosis is given.

The Drosophila melanogaster glucuronyltransferases dGlcAT-S and dGlcAT-P were reported to be expressed ubiquitously and results of in vitro activity assays indicate a functional redundancy. We analyzed both transferases in vivo and in vitro and could show significant differences in their activity towards N-and O-glycoproteins in vivo. While GlcAT-P is able to use N-linked N-acetyllactosamine chains and the O-linked T-antigen as a substrate to form non-sulfated HNK1- (GlcAβ1-3Galβ1-4GlcNAcβ1-) and glucuronyl-T-antigens in vivo, GlcAT-S adds glucuronic acid only to N-linkedchains, thereby synthesizing only the non-sulfated HNK1-antigen.

Adolescence is a period of development characterized by numerous neurobiological changes that significantly influence behavior and brain function. Adolescence is of particular interest due to the alarming statistics indicating that mortality rates increase two to three-fold during this time compared to childhood, due largely to a peak in risk-taking behaviors resulting from increased impulsivity and sensation seeking. Furthermore, there exists large unexplained variability in these behaviors that are in part mediated by biological factors. Recent advances in molecular genetics and functional neuroimaging have provided a unique and exciting opportunity to noninvasively study the influence of genetic factors on brain function in humans. While genes do not code for specific behaviors, they do determine the structure and function of proteins that are essential to the neuronal processes that underlie behavior. Therefore, studying the interaction of genotype with measures of brain function over development could shed light on critical time points when biologically mediated individual differences in complex behaviors emerge. Here we review animal and human literature examining the neurobiological basis of adolescent development related to dopamine neurotransmission. Dopamine is of critical importance because of (1) its role in cognitive and affective behaviors, (2) its role in the pathogenesis of major psychopathology, and (3) the protracted development of dopamine signaling pathways over adolescence. We will then focus on current research examining the role of dopamine-related genes on brain function. We propose the use of imaging genetics to examine the influence of genetically mediated dopamine variability on brain function during adolescence, keeping in mind the limitations of this approach. PMID:24139694

Experiments were performed to determine whether both H and L chains of different anti-native DNA autoantibodies are uniformly involved in binding to DNA. Two purified monoclonal mouse (MRL-1pr/1pr) IgG autoantibodies, H241 and 2C10, were tested. They both bound synthetic helical oligonucleotides of 10 to 20 base pairs in a gel electrophoresis retardation assay but differed in their preferences for given base sequences. Exposure of antibody-radiolabeled oligonucleotide mixtures to UV light (254 nm) for 10 min led to specific covalent cross-linking of oligonucleotide to both the H and the L chains of H241 but only to the H chain of 2C10. Single labeling events were detected without higher aggregation. The oligonucleotides were not cross-linked to unrelated IgG, even after 2 h of irradiation. Cross-linked (radioactively labeled) H and L chains of H241 and 2C10 were isolated from denaturing electrophoresis gels and digested with lysyl endopeptidase and/or staphylococcal V8 protease. H241 and 2C10 H chains each yielded a major labeled peptide fragment, but the peptides from the two antibodies were different. These experiments measured only some of the antibody-DNA interactions, probably with bases in the major groove of the DNA. They indicated that two MRL-1pr/1pr IgG anti-native DNA antibodies differ in their H and L chain contacts with DNA and provide an approach to identifying affinity-labeled binding sites in the antibodies.

We examined the link between household chaos (i.e., noise, clutter, disarray, lack of routines) and maternal executive function (i.e., effortful regulation of attention and memory), and whether it varied as a function of socioeconomic risk (i.e., single parenthood, lower mother and father educational attainment, housing situation, and father unemployment). We hypothesized that: 1) higher levels of household chaos would be linked with poorer maternal executive function, even when controlling f...

Full Text Available The behavior of a hard sphere fluid in slit-like pores with walls modified by grafted chain molecules composed of hard sphere segments is studied using density functional theory. The chains are grafted to opposite walls via terminating segments forming pillars. The effects of confinement and of "chemical" modification of pore walls on the entropic solvation force are investigated in detail. We observe that in the absence of adsorbed fluid the solvation force is strongly repulsive for narrow pores and attractive for wide pores. In the presence of adsorbed fluid both parts of the curve of the solvation force may develop oscillatory behavior dependent on the density of pillars, the number of segments and adsorption conditions. Also, the size ratio between adsorbed fluid species and chain segments is of importance for the development of oscillations. The choice of these parameters is crucial for efficient manipulation of the solvation force as desired for pores of different width.

Over the last decade, supply chain management has become a recognized strategic tool\\ud to ensure customer satisfaction (Chopra and Meindl, 2004). Strategic supply chain\\ud management improves the way processes are done and hence improves long-term\\ud performance (Harrison and Van Hoek, 2005). Evaluating the performance of supply\\ud chain (SC) operations can contribute to redesigning business goals and strategies\\ud through assessing the current SC operations’ performance in order to identify...

The current study extended research on working memory, attention shifting, and inhibitory control problems –indicated as executive functions (EF) – that may play a role in acquiring early literacy and numeracy skills. Four research questions were targeted: 1. Do EF skills interfere with benefiting

We argue, by analogy to the neural organization of the object recognition system, that demonstration of modulation of mirror neurons by associative learning does not imply absence of genetic adaptation. Innate connectivity defines the types of processes mirror neurons can participate in while allowing for extensive local plasticity. However, the proper function of these neurons remains to be worked out.

The XX0 Heisenberg model on a cyclic chain is considered. The representation of the Bethe wave functions via the Schur functions allows to apply the well-developed theory of the symmetric functions to the calculation of the thermal correlation functions. The determinantal expressions of the form-factors and of the thermal correlation functions are obtained. The q-binomial determinants enable the connection of the form-factors with the generating functions both of boxed plane partitions and of self-avoiding lattice paths. The asymptotical behavior of the thermal correlation functions is studied in the limit of low temperature provided that the characteristic parameters of the system are large enough.

The XX0 Heisenberg model on a cyclic chain is considered. The representation of the Bethe wave functions via the Schur functions allows to apply the well-developed theory of the symmetric functions to the calculation of the thermal correlation functions. The determinantal expressions of the form-factors and of the thermal correlation functions are obtained. The q-binomial determinants enable the connection of the form-factors with the generating functions both of boxed plane partitions and of self-avoiding lattice paths. The asymptotical behavior of the thermal correlation functions is studied in the limit of low temperature provided that the characteristic parameters of the system are large enough.

Intein-mediated expressed protein ligation (EPL) permits the site-specific chemical customization of proteins. While traditional techniques have used purified, soluble proteins, we have extended these methods to release and modify intein fusion proteins expressed on the yeast surface, thereby eliminating the need for soluble protein expression and purification. To this end, we sought to simultaneously release yeast surface-displayed proteins and selectively conjugate with chemical functionalities compatible with EPL and click chemistry. Single-chain antibodies (scFv) and green fluorescent protein (GFP) were displayed on the yeast surface as fusions to the N-terminus of the Mxe GyrA intein. ScFv and GFP were released from the yeast surface with either a sulfur nucleophile (MESNA) or a nitrogen nucleophile (hydrazine) linked to an azido group. The hydrazine azide permitted the simultaneous release and azido functionalization of displayed proteins, but nonspecific reactions with other yeast proteins were detected, and cleavage efficiency was limited. In contrast, MESNA released significantly more protein from the yeast surface while also generating a unique thioester at the carboxy-terminus of the released protein. These protein thioesters were subsequently reacted with a cysteine alkyne in an EPL reaction and then employed in an azide-alkyne cycloaddition to immobilize the scFv and GFP on an azide-decorated surface with >90% site-specificity. Importantly, the immobilized proteins retained their activity. Since yeast surface display is also a protein engineering platform, these approaches provide a particularly powerful tool for the rapid assessment of engineered proteins.

Genome-wide association studies have revealed a multitude of breast cancer-associated SNPs. The majority of these SNPs are located in noncoding regions of the genome. Yet how they contribute to breast cancer development is unknown. Recently, a groundbreaking study by the Lupien group has shown that risk-associated SNPs of breast cancer are enriched for FOXA1 binding sites, which influences the function of this transcription factor.

Cell surface CD147 shows remarkable variations in size (31-65 kDa) because of heterogeneous N-glycosylation, with the most highly glycosylated forms functioning to induce matrix metalloproteinase (MMP) production. Here we show that all three CD147 N-glycosylation sites make similar contributions to both high and low glycoforms (HG- and LG-CD147). l-Phytohemagglutinin lectin binding and swainsonine inhibition experiments indicated that HG-CD147 contains N-acetylglucosaminyltransferase V-cataly...

Ubiquitin (Ub) can generate versatile molecular signals and lead to different celluar fates. The functional poly-valence of Ub is believed to be resulted from its ability to form distinct polymerized chains with eight linkage types. To provide a full picture of ubiquitin code, we explore the binding landscape of two free Ub monomers and also the functional landscapes of of all eight linkage types by theoretical modeling. Remarkably, we found that most of the compact structures of covalently connected dimeric Ub chains (diUbs) pre-exist on the binding landscape. These compact functional states were subsequently validated by corresponding linkage models. This leads to the proposal that the folding architecture of Ub monomer has encoded all functional states into its binding landscape, which is further selected by different topologies of polymeric Ub chains. Moreover, our results revealed that covalent linkage leads to symmetry breaking of interfacial interactions. We further propose that topological constraint not only limits the conformational space for effective switching between functional states, but also selects the local interactions for realizing the corresponding biological function. Therefore, the topological constraint provides a way for breaking the binding symmetry and reaching the functional specificity. The simulation results also provide several predictions that qualitatively and quantitatively consistent with experiments. Importantly, the K48 linkage model successfully predicted intermediate states. The resulting multi-state energy landscape was further employed to reconcile the seemingly contradictory experimental data on the conformational equilibrium of K48-diUb. Our results further suggest that hydrophobic interactions are dominant in the functional landscapes of K6-, K11-, K33- and K48 diUbs, while electrostatic interactions play a more important role in the functional landscapes of K27, K29, K63 and linear linkages. PMID:24992446

Using first-principles density functional theory and nonequilibrium Green's function formalism, we investigate theoretically how the twist of torsional angle effect on the electronic transport properties of the diphenylacetylene (DPA) molecule bridged between a (5,5) capped carbon nanotubes (CCNTs) and linear carbon atomic chains. The tunneling current through the (5,5) capped CNT-DPA-linear carbon atomic chain system was found larger current when the torsional angle is 0° (coplanar conformation). BY increasing the torsional angle equal to 90° (perpendicular conformation), between two benzene rings, the current is strongly suppressed. These results suggest that the (5,5) capped CNT-DPA-linear carbon atomic chain system is a potential candidate for molecular switches. The physical origin of the switching behavior of the (5,5) capped CNT-DPA-linear carbon atomic chain system is systematically studied by analyses of transmission spectrum, energy gaps, the spatial distribution of frontier molecular orbital and current-voltage characteristics of the systems.

Full Text Available Key factors of outsourcing strategies include cost and capacity flexibility. Cost saving and capacity flexibility depend on the connection between product characteristics and the supply chain network. Functional products involve efficient supply chains. Fashion products should move in the production and distribution system as quickly as possible in which maximum capacity flexibility provides a responsive supply chain. Moreover, complex products with global parts sourcing involve comparatively more risk. This paper evaluates an outsourcing strategies considering functional and fast fashion products in the textile supply chain. There are four categories of production options. Textile manufacturer receives production contracts at in-house facility in home country. Capacity flexibility is measured as the combination of destinations with maximum capacity. Product complexity risk is incorporated as the number of parts/components sourced domestically and internationally at each production destination. A multi-objective model for outsourcing strategiesis proposed based on operational cost, capacity flexibility, and product complexity risk. The model is solved using three variants of goal programming. Based on the results, several insights are proposed for outsourcing decision making.

T. Dobzhansky (1973) has been credited with saying: 'nothing in biology makes sense, except in the light of evolution'. The evolutionary conservation of gene function, as well as remarkable conservation of elemental behavioral mechanisms, guarantees that much of what we learn in one organism will inform our understanding of behavior in all animals, including humans. This insight has permitted behavior-geneticists to choose organisms based on experimental tractability for a given scientific question. IBANGS as a society has clearly embraced this Dobzhanskian worldview. As a result, the intellectual synergy of cross-species behavior-genetic analysis was palpable at the IBANGS meeting in Tours, France.

The study of the structural basis of gas exchange function in the lung depends on the availability of quantitative information that concerns the structures establishing contact between the air in the alveoli and the blood in the alveolar capillaries, which can be entered into physiological equations for predicting oxygen uptake. This information is provided by morphometric studies involving stereological methods and allows estimates of the pulmonary diffusing capacity of the human lung that agree, in experimental studies, with the maximal oxygen consumption. The basis for this "machine lung" structure lies in the complex design of the cells building an extensive air-blood barrier with minimal cell mass.

In this thesis, we have demonstrated a very useful and simple method (one-pot polymerization process) for synthesis of chain end functionalized polypropylene. The chemistry involves a chain transfer reaction to a styrenic derivative (St-f), with or without hydrogen during propylene polymerization, using an Exxon-Hoechst C2-symmetric catalyst (rac-Me 2Si[2-Me-4-Ph(Ind)]2ZrCl2/MAO complex) or a Mitsubishi C1-symmetric catalyst (Me2Si(2-Me-Benz[e]Ind(2-Me-4-Ph-4HAzu)HfCl 2 with MAO or trialkylaluminum-treated clay). In the presence of the Exxon-Hoechst catalyst, the propylene propagating chain-end engages in a facile consecutive chain transfer reaction, reacting with St-f and then with hydrogen, with high catalytic activity under the proper reaction conditions. The polymer molecular weight is proportional to the molar ratio of [propylene]/[St-f]. A silane protecting group in St-NSi2 or St-OSi unit can be hydrolyzed in an acidic solution during the sample work-up step to obtain desirable i-PP polymers, such as i-PP with a terminal NH2 or OH group, in one pot. Despite the low concentration, the terminal functional group is very reactive and can serve as an active site for many applications. One example was shown in a chain extension reaction (coupling reaction) with polycaprolactone (PCL) in solution to form PP-b-PCL diblock copolymers that are very effective compatibilizers in PP/PCL polymer blends. Unexpectedly, a Mitsubishi C1-symmetric catalyst exhibits significant polymerization activity even in the absence of hydrogen, indicating that the trialkylaluminum may participate in chain transfer to p-MS (p-methylstyrene) terminated propagating chains. In the case of polymerization using MAO as a cocatalyst at 55°C, the addition of hydrogen increases the activity and regulates the polymer molecular weight. The chain-end structure is solely terminal p-MS. When TEA (triethylaluminium) -treated clay is adopted as an activator and carrier at the optimal polymerization

. In order to implement the traceability ofthe manufacturing process, the geometry and dimension of the micro structure on the tool and the replica were assessed viametrological methods. The functionality of the anisotropic surfaces on the polymer replicas were evaluated by a gonioreflectometerand image......This paper aims to introduce a process chain for fabrication of anisotropic optical functional surfaces on polymer products. Thesurface features under investigation are composed of micro serrated ridges. The scope was to maximize the visible contrast betweenhorizontally orthogonal textured surfaces...... from a certain viewing angle. The process chain comprised three steps: tooling, replicationand quality assurance. Tooling was achieved by precision micro milling. Replication processes such as injection moulding, hotembossing, blow moulding, etc. were employed according to the specific type of product...

Full Text Available Sex differences are well known to be determinants of development, health and disease. Epigenetic mechanisms are also known to differ between men and women through X-inactivation in females. We hypothesized that epigenetic sex differences may also result from sex hormone functions, in particular from long-lasting androgen programming. We aimed at investigating whether inactivation of the androgen receptor, the key regulator of normal male sex development, is associated with differences of the patterns of DNA methylation marks in genital tissues. To this end, we performed large scale array-based analysis of gene methylation profiles on genomic DNA from labioscrotal skin fibroblasts of 8 males and 26 individuals with androgen insensitivity syndrome (AIS due to inactivating androgen receptor gene mutations. By this approach we identified differential methylation of 167 CpG loci representing 162 unique human genes. These were significantly enriched for androgen target genes and low CpG content promoter genes. Additional 75 genes showed a significant increase of heterogeneity of methylation in AIS compared to a high homogeneity in normal male controls. Our data show that normal and aberrant androgen receptor function is associated with distinct patterns of DNA-methylation marks in genital tissues. These findings support the concept that transcription factor binding to the DNA has an impact on the shape of the DNA methylome. These data which derived from a rare human model suggest that androgen programming of methylation marks contributes to sexual dimorphism in the human which might have considerable impact on the manifestation of sex-associated phenotypes and diseases.

An enigma of modern medicine has persisted for over 150 years. The mechanisms by which volatile anesthetics (VAs) produce their effects (loss of consciousness, analgesia, amnesia, and immobility) remain an unsolved mystery. Many attractive putative molecular targets have failed to produce a significant effect when genetically tested in whole-animal models [1-3]. However, mitochondrial defects increase VA sensitivity in diverse organisms from nematodes to humans [4-6]. Ndufs4 knockout (KO) mice lack a subunit of mitochondrial complex I and are strikingly hypersensitive to VAs yet resistant to the intravenous anesthetic ketamine [7]. The change in VA sensitivity is the largest reported for a mammal. Limiting NDUFS4 loss to a subset of glutamatergic neurons recapitulates the VA hypersensitivity of Ndufs4(KO) mice, while loss in GABAergic or cholinergic neurons does not. Baseline electrophysiologic function of CA1 pyramidal neurons does not differ between Ndufs4(KO) and control mice. Isoflurane concentrations that anesthetize only Ndufs4(KO) mice (0.6%) decreased the frequency of spontaneous excitatory postsynaptic currents (sEPSCs) only in Ndufs4(KO) CA1 neurons, while concentrations effective in control mice (1.2%) decreased sEPSC frequencies in both control and Ndufs4(KO) CA1 pyramidal cells. Spontaneous inhibitory postsynaptic currents (sIPSCs) were not differentially affected between genotypes. The effects of isoflurane were similar on evoked field excitatory postsynaptic potentials (fEPSPs) and paired pulse facilitation (PPF) in KO and control hippocampal slices. We propose that CA1 presynaptic excitatory neurotransmission is hypersensitive to isoflurane in Ndufs4(KO) mice due to the inhibition of pre-existing reduced complex I function, reaching a critical reduction that can no longer meet metabolic demands.

This paper describes five growth points in linking representations of function developed from a study of secondary school learners. Framed within the cognitivist perspective and process-object conception of function, the growth points were identified and described based on linear and quadratic function tasks learners can do and their strategies…

In this paper, a three species food chain model, consisting of a hybrid type of prey-dependent and predator-dependent functional responses, is investigated analytically as well as numerically. The local and global stability analysis is carried out. The persistence conditions are established. Bifurcation diagrams are obtained for biologically feasible parameters. The results show that the system exhibits rich complexity features such as stable, periodic and chaotic dynamics.

Several methods for evaluating the sublayer suspension beneath old pavement with falling weight deflectormeter(FWD), were summarized and the respective advantages and disadvantages were analyzed. Based on these methods, the evaluation principles were improved and a new type of the neural network, functional-link neural network was proposed to evaluate the sublayer suspension with FWD test results. The concept of functionlink, learning method of functional-link neural network and the establishment process of neural network model were studied in detail. Based on the old pavement over-repairing engineering of Kaiping section, Guangdong Province in G325 National Highway, the application of functional-link neural network in evaluation of sublayer suspension beneath old pavement based on FWD test data on the spot was investigated. When learning rate is 0.1 and training cycles are 405, the functional-link network error is less than 0.0001, while the optimum chosen 4-8-1 BP needs over 10000 training cycles to reach the same accuracy with less precise evaluation results. Therefore, in contrast to common BP neural network,the functional-link neural network adopts single layer structure to learn and calculate, which simplifies the network, accelerates the convergence speed and improves the accuracy. Moreover the trained functional-link neural network can be adopted to directly evaluate the sublayer suspension based on FWD test data on the site. Engineering practice indicates that the functional-link neural model gains very excellent results and effectively guides the pavement over-repairing construction.

this modification of the interfacial region could specifically control the mechanical properties. By considering two different grafting densities, the effect of dipolar forces across the nanopore with increasing load was addressed. In general, it was found that interfacial viscosities and friction forces increase......Nonequilibrium molecular dynamics simulations were performed to probe structural and dynamical properties of tail-grafted, amphiphilic chains under shear at different grafting densities. Emphasis was put on the modification of the head groups in order to investigate to which extent...

Protein cross-linking via the Maillard reaction with alpha-dicarbonyl compounds has been the subject of intense scrutiny in the literature. We report here a study of the impact of this cross-linking on enzyme function. Protein function following glycation was examined by treating ribonuclease A with methylglyoxal, glyoxal, and diacetyl, which cross-linked the enzyme and impaired its activity. The effects of two reported Maillard reaction inhibitors, aminoguanidine and 3,5-dimethylpyrazole-1-carboxamidine, on the cross-linking reaction were assessed, with a parallel measurement of the effect on enzyme activity. The results demonstrate that preventing protein cross-linking does not necessarily preserve enzyme activity. These results cast doubt on the likely efficacy of some purported antiaging compounds in vivo.

Full Text Available The algorithm of simulating the trophic net in a system consisted of 1 producer and 8 consumer species, which linked by 14 trophic relations, using Microsoft Excel is presented. Dynamics of productivity and biomass consumption in the model system are analyzed. Regularities of consortium nets functioning are stated.

Full Text Available Potassium channels have been found in the inner mitochondrial membranes of various cells. These channels regulate the mitochondrial membrane potential, the matrix volume and respiration. The activation of these channels is cytoprotective. In our study, the single-channel activity of a large-conductance Ca(2+-regulated potassium channel (mitoBKCa channel was measured by patch-clamping mitoplasts isolated from the human astrocytoma (glioblastoma U-87 MG cell line. A potassium-selective current was recorded with a mean conductance of 290 pS in symmetrical 150 mM KCl solution. The channel was activated by Ca(2+ at micromolar concentrations and by the potassium channel opener NS1619. The channel was inhibited by paxilline and iberiotoxin, known inhibitors of BKCa channels. Western blot analysis, immuno-gold electron microscopy, high-resolution immunofluorescence assays and polymerase chain reaction demonstrated the presence of the BKCa channel β4 subunit in the inner mitochondrial membrane of the human astrocytoma cells. We showed that substrates of the respiratory chain, such as NADH, succinate, and glutamate/malate, decrease the activity of the channel at positive voltages. This effect was abolished by rotenone, antimycin and cyanide, inhibitors of the respiratory chain. The putative interaction of the β4 subunit of mitoBKCa with cytochrome c oxidase was demonstrated using blue native electrophoresis. Our findings indicate possible structural and functional coupling of the mitoBKCa channel with the mitochondrial respiratory chain in human astrocytoma U-87 MG cells.

We present a theoretical framework for understanding the wave functions and spectrum of an extensively studied paradigm for quasiperiodic systems, namely the Fibonacci chain. Our analytical results, which are obtained in the limit of strong modulation of the hopping amplitudes, are in good agreement with published numerical data. In the perturbative limit, we show a symmetry of wave functions under permutation of site and energy indices. We compute the wave-function renormalization factors and from them deduce analytical expressions for the fractal exponents corresponding to individual wave functions, as well as their global averages. The multifractality of wave functions is seen to appear at next-to-leading order in ρ . Exponents for the local spectral density are given, in extremely good accord with numerical calculations. Interestingly, our analytical results for exponents are observed to describe the system rather well even for values of ρ well outside the domain of applicability of perturbation theory.

The half-infinite XXZ spin chain with a triangular boundary is considered in the massive regime. Two integral representations of correlation functions are proposed using bosonization. Sufficient conditions such that the expressions for triangular boundary conditions coincide with those for diagonal boundary conditions are identified. As an application, summation formulae of the boundary expectation values $\\langle \\sigma_1^a\\rangle $ with $a=z,\\pm$ are obtained. Exploiting the spin-reversal property, relations between $n$-fold integrals of elliptic theta functions are extracted.

Full Text Available Side-chain oligo- and polyglutamylation represents an important posttranslational modification in tubulin physiology. The particular number of glutamate units is related to specific regulatory functions. In this work, we present a method for the synthesis of building blocks for the Fmoc synthesis of peptides containing main chain glutamic acid residues that carry side-chain branching with oligo-glutamic acid. The two model peptide sequences CYEEVGVDSVEGEG-E(E-EEGEEY and CQDATADEQG-E(E-FEEEEGEDEA from the C-termini of mammalian α1- and β1-tubulin, respectively, containing oligo-glutamic acid side-chain branching with lengths of 1 to 5 amino acids were assembled in good yield and purity. The products may lead to the generation of specific antibodies which should be important tools for a more detailed investigation of polyglutamylation processes.

Full Text Available Innovative synthetic approaches should be simple and environmentally friendly. Here, we present the surface modification of inorganic submicrometer particles with long alkyl chain organophosphorus coupling agents without the need of a solvent, which makes the technique environmentally friendly. In addition, it is of great benefit to realize two goals in one step: size reduction and, simultaneously, surface functionalization. A top-down approach for the synthesis of metal oxide particles with in situ surface functionalization is used to modify titania with long alkyl chain organophosphorus coupling agents. A high energy planetary ball mill was used to perform reactive milling using titania as inorganic pigment and long alkyl chain organophosphorus coupling agents like dodecyl and octadecyl phosphonic acid. The final products were characterized by IR, NMR and X-ray fluorescence spectroscopy, thermal and elemental analysis as well as by X-ray powder diffraction and scanning electron microscopy. The process entailed a tribochemical phase transformation from the starting material anatase to a high-pressure modification of titania and the thermodynamically more stable rutile depending on the process parameters. Furthermore, the particles show sizes between 100 nm and 300 nm and a degree of surface coverage up to 0.8 mmol phosphonate per gram.

In order to perform a fundamental study of platelet substitutes, novel particles that bound to activated platelets were prepared using two oligopeptides conjugated to latex beads. The oligopeptides were CHHLGGAKQAGDV (H12), which is a fibrinogen gamma-chain carboxy-terminal sequence (gamma 400-411), and CGGRGDF (RGD), which contains a fibrinogen alpha-chain sequence (alpha 95-98 RGDF). Both peptides contained an additional amino-terminal cysteine to enable conjugation. Human serum albumin was adsorbed onto the surface of latex beads (average diameter 1microm) and pyridyldisulfide groups were chemically introduced into the adsorbed protein. H12 or RGD peptides were then chemically linked to the modified surface protein via disulfide linkages. H12- or RGD-conjugated latex beads prepared in this way enhanced the in vitro thrombus formation of activated platelets on collagen-immobilized plates under flowing thrombocytopenic-imitation blood. Based on the result of flow cytometric analyses of agglutination, PAC-1 binding, antiP-selectin antibody binding, and annexin V binding, the H12-conjugated latex beads showed minimal interaction with non-activated platelets. These results indicate the excellent potential of H12-conjugated particles as a candidate for a platelet substitute.

Semi-crystalline microparticles of inulin (MPI) have clinical utility as potent human vaccine adjuvants but their relevant surface structure and crystal assembly remain undefined. We show inulin crystal surfaces to resemble multi-layered, discoid radial spherulites resulting from very rapid formation of complex tertiary structures, implying directed crystal initiation. Physical and in silico molecular modelling of unit cells confirm steric feasibility of initiation by hydrogen-bonded cross-linking of terminal glucose to a fructose of another chain, mimicking bonding in sucrose crystals. A strong, chelate-like dual H-bond is proposed to compel the known antiparallel alignment of inulin chains. Such cross-linking would require one extra fructose per chain in the native inulin crystal, as observed. Completion of five H-bonded internal ring-domains would 'lock in' each new 6-fructose structural unit of each antiparallel helix pair to create a new isoform. All known properties of inulin isoforms follow readily from these concepts.

The overarching goal presented in this thesis is the self-assembly of synthetic systems into higher ordered structures utilizing supramolecular chemistry. Noncovalent interactions including charge-transfer and hydrogen bonding as well as DNA hybridization are exploited to induce the assembly of polymers and colloids into well-defined architectures. This strategy provides a tunable handle on materials bulk properties that can be adjusted by simply changing variables such as temperature and solvent. A brief overview of design principles for the supramolecular assembly of side-chainfunctionalized polymers is presented. The polymerization technique selected was living ring-opening metathesis polymerization (ROMP), thus affording control over molecular weight and molecular weight distributions. ROMP also allowed for the incorporation of functional groups that were used to assemble the polymers into ordered structures. Charge-transfer motifs were exploited and shown to drive the assembly of random and alternating copolymers via intramolecular side-chain interactions. Incorporation of complementary hydrogen bonding motifs was shown to guide the single-chain folding of a multifunctional triblock copolymer into sheet-like structures. Precision over the size, shape, and monomer sequence were identified as key elements for efficient self-assembly. The self-assembly of colloids using DNA hybridization was also investigated. Previously, the majority of colloid-based research relied upon the self-assembly of spherical isotropic particles into closed-packed arrangements. In contrast, anisotropic particles may allow for the realization of open structures. By expanding upon a method to permanently cross-link DNA strands incubated on a colloidal surface, a new strategy to engineer patchy particles is described. These functional DNA-coated patches are demonstrated to direct particle assembly. The self-assembly of polymer and colloidal systems utilizing noncovalent interactions

We propose a density functional theory to describe adsorption of Lennard-Jones fluid in slitlike pores modified by chain molecules. Specifically, the chains are bonded by their ends to the opposite pore walls, so they can form pillaredlike structure. Two models are studied. In the first model, the nonterminating segments of chains can change their configuration inside the pore upon adsorption of spherical species. In the second model, the chains configuration remains fixed, so that the system is similar to a nonuniform quenched-annealed mixture. We study capillary condensation of fluid species inside such modified pores and compare the results obtained for two models.

The one-dimensional fall of a folded chain with one end suspended from a rigid support and a chain falling from a resting heap on a table is studied. Because their Lagrangians contain no explicit time dependence, the falling chains are conservative systems. Their equations of motion are shown to contain a term that enforces energy conservation when masses are transferred between subchains. We show that Cayley's 1857 energy nonconserving solution for a chain falling from a resting heap is incorrect because it neglects the energy gained when a link leaves a subchain. The maximum chain tension measured by Calkin and March for the falling folded chain is given a simple if rough interpretation. Other aspects of the falling folded chain are briefly discussed.

The primary objectives of this research were twofold: (1) development of synthetic procedures for combining quasiliving carbocationic polymerization (QLCCP) of isobutylene (IB) and reversible addition fragmentation chain transfer (RAFT) polymerization for block copolymer synthesis; (2) utilization of efficient, robust, and modular chemistries for facile functionalization of polyisobutylene (PIB). In the first study block copolymers consisting of PIB, and either PMMA or PS block segments, were synthesized by a site transformation approach combining living cationic and reversible addition-fragmentation chain transfer (RAFT) polymerizations. The initial PIB block was synthesized via quasiliving cationic polymerization using the TMPCl/TiCl4 initiation system and was subsequently converted into a hydroxylterminated PIB. Site transformation of the hydroxyl-terminated PIB into a macro chain transfer agent (PIB-CTA) was accomplished by N,N'-dicyclohexylcarbodiimide/dimethylaminopyridine-catalyzed esterification with 4-cyano-4-(dodecylsulfanylthiocarbonylsulfanyl)pentanoic acid. In the second study another site transformation approach was developed to synthesize a novel block copolymer, composed of PIB and PNIPAM segments. The PIB block was prepared via quasiliving cationic polymerization and end functionalized by in-situ quenching to yield telechelic halogen-terminated PIB. Azido functionality was obtained by displacement of the terminal halogen through nucleophilic substitution, which was confirmed by both 1H and 13C NMR. Coupling of an alkyne-functionalchain transfer agent (CTA) to azido PIB was successfully accomplished through a copper catalyzed click reaction. Structure of the resulting PIB-based macro-CTA was verified with 1H NMR, FTIR, and GPC; whereas coupling reaction kinetics were monitored by real time variable temperature (VT) 1H NMR. In a third study, a click chemistry functionalization procedure was developed based upon the azide-alkyne 1,3-dipolar

Full Text Available Dozens of broadly neutralizing HIV-1 antibodies have been isolated in the last few years from the sera of HIV-1-infected individuals. Only a limited number of regions on the HIV-1 spike, however, are recognized by these antibodies. One of these regions (N332 is characterized by an N-linked glycan at residue 332 on HIV-1 gp120 and is recognized by antibody 2G12 and by the recently reported antibodies PGT121-137, the latter isolated from three donors. To investigate the diversity in mode of antibody recognition at the N332 site, we used functional complementation between antibody heavy and light chains as a means of assessing similarity in mode of recognition. We examined a matrix of 12 PGT-heavy chains with each of 12 PGT-light chains. Expression in 96-well format for the 144 antibodies (132 chimeric and 12 wild-type was generally consistent (58 ± 10 µg/ml. In contrast, recognition of HIV-1 gp120 was bimodal: when the source of heavy and light chains was from the same donor, recognition was good; when sources of heavy and light chains were from different donors, recognition was poor. Moreover, neutralization of HIV-1 strains SF162.LS and TRO.11 generally followed patterns of gp120 recognition. These results are consistent with published sequence, mutational, and structural findings, all of which indicate that N332-directed neutralizing antibodies from different donors utilize different modes of recognition, and provide support for a correlation between functional complementation of antibody heavy and light chains and similarity in antibody mode of recognition. Overall, our results add to the growing body of evidence that the human immune system is capable of recognizing the N332-region of HIV-1 gp120 in diverse ways.

Full Text Available NK cells are components of the innate immunity system and play an important role as a first-line defense mechanism against viral infections and in tumor immune surveillance. Their development and their functional activities are controlled by several factors among which cytokines sharing the usage of the common cytokine-receptor gamma chain play a pivotal role. In particular, IL-2, IL-7, IL-15, and IL-21 are the members of this family predominantly involved in NK cell biology. In this paper, we will address their role in NK cell ontogeny, regulation of functional activities, development of specialized cell subsets, and acquisition of memory-like functions. Finally, the potential application of these cytokines as recombinant molecules to NK cell-based immunotherapy approaches will be discussed.

Polyunsaturated fatty acids such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) occur in biological membranes as acyl groups of phospholipids and exhibit remarkable physiological activities. In human, they have various beneficial effects on health such as protective effects against cardiovascular disease, inflammation, and cancer. We have been studying their physiological functions in bacteria, which have a much simpler membrane structure than eukaryotes. We found that the cell division of a marine bacterium, Shewanella livingstonensis Ac10, is inhibited and shows growth retardation by disruption of its EPA biosynthesis genes. We synthesized a fluorescent analog of EPA-containing phospholipids (EPA-PLs) as a chemical probe to analyze their subcellular distribution and found that it is localized at the center of the cell undergoing cell division. This localization was shown to depend on the structure of the hydrocarbon chain of the phospholipids. We also examined the effects of EPA-PLs on the folding of Omp74, a major membrane protein of this bacterium, by using liposomes and found that EPA-PLs facilitated the folding process. The results imply that EPA-PLs function as a chemical chaperone in the folding of membrane proteins. These findings would contribute to understanding of the physiological function of phospholipids with polyunsaturated fatty acyl chains in various biological membranes.

The nutritional and pharmaceutical values of long-chain polyunsaturated fatty acids (LC-PUFAs) such as arachidonic, eicosapentaenoic and docosahexaenoic acids have been well recognized. These LC-PUFAs are physiologically important compounds in bacteria and eukaryotes. Although little is known about the biosynthetic mechanisms and functions of LC-PUFAs in bacteria compared to those in higher organisms, a combination of genetic, bioinformatic, and molecular biological approaches to LC-PUFA-producing bacteria and some eukaryotes have revealed the notably diverse organization of the pfa genes encoding a polyunsaturated fatty acid synthase complex (PUFA synthase), the LC-PUFA biosynthetic processes, and tertiary structures of the domains of this enzyme. In bacteria, LC-PUFAs appear to take part in specific functions facilitating individual membrane proteins rather than in the adjustment of the physical fluidity of the whole cell membrane. Very long chain polyunsaturated hydrocarbons (LC-HCs) such as hentriacontanonaene are considered to be closely related to LC-PUFAs in their biosynthesis and function. The possible role of LC-HCs in strictly anaerobic bacteria under aerobic and anaerobic environments and the evolutionary relationships of anaerobic and aerobic bacteria carrying pfa-like genes are also discussed.

Full Text Available The nutritional and pharmaceutical values of long-chain polyunsaturated fatty acids (LC-PUFAs such as arachidonic, eicosapentaenoic and docosahexaenoic acids have been well recognized. These LC-PUFAs are physiologically important compounds in bacteria and eukaryotes. Although little is known about the biosynthetic mechanisms and functions of LC-PUFAs in bacteria compared to those in higher organisms, a combination of genetic, bioinformatic, and molecular biological approaches to LC-PUFA-producing bacteria and some eukaryotes have revealed the notably diverse organization of the pfa genes encoding a polyunsaturated fatty acid synthase complex (PUFA synthase, the LC-PUFA biosynthetic processes, and tertiary structures of the domains of this enzyme. In bacteria, LC-PUFAs appear to take part in specific functions facilitating individual membrane proteins rather than in the adjustment of the physical fluidity of the whole cell membrane. Very long chain polyunsaturated hydrocarbons (LC-HCs such as hentriacontanonaene are considered to be closely related to LC-PUFAs in their biosynthesis and function. The possible role of LC-HCs in strictly anaerobic bacteria under aerobic and anaerobic environments and the evolutionary relationships of anaerobic and aerobic bacteria carrying pfa-like genes are also discussed.

Objective To study the effect of 4-6 weeks' treadmill training of male SD rats on the contractile function of their gastrocnemius myosin heavy chain (MHC). Methods Forty male SD rats were randomly divided into control group and training group. The treadmill training of the training group rats was incessantly performed for 4-6 weeks at an intensity of about 75% VO2max (18.5-24 m/min,gradient of 0°,each training session lasting 50 minutes,twice a day). The content of gastrocnemius MHC mRNA was tested by rever...

This paper deals with the behavior of positive solutions to a reaction-diffusion system with homogeneous Neumann boundary conditions describing a three species food chain. A sufficient condition for the local asymptotical stability is given by linearization and also a sufficient condition...... for the global asymptotical stability is given by a Lyapunov function. Our result shows that the equilibrium solution is globally asymptotically stable if the net birth rate of the first species is big enough and the net death rate of the third species is neither too big nor too small. (C) 2004 Elsevier Ltd. All...

The process stability of biogas plants is often deteriorated by the accumulation of Long Chain Fatty Acids (LCFA). The microbial community shifts due to LCFA disturbances have been poorly understood as the molecular techniques used were not able to identify the genome characteristics of uncultured...... microorganisms, and additionally, the presence of limited number of reference genomes in public databases prevented the comprehension of specific functional roles characterizing these microorganisms. The present study is the first research which deciphers by means of high throughput shotgun sequencing...

NK cells are components of the innate immunity system and play an important role as a first-line defense mechanism against viral infections and in tumor immune surveillance. Their development and their functional activities are controlled by several factors among which cytokines sharing the usage of the common cytokine-receptor gamma chain play a pivotal role. In particular, IL-2, IL-7, IL-15, and IL-21 are the members of this family predominantly involved in NK cell biology. In this paper, w...

Spin chains are the basic elements of integrable quantum models. These models have direct applications in condense matter theory, in statistical physics, in quantum optics, in field theory and even in string theory but they are also important because they enable us to solve, in an exact manner, non-perturbative phenomena that otherwise would stay unresolved. The method described in this work is based on the algebraic Bethe Ansatz. It is shown how this method can be used for the computation of null temperature correlation functions of the Heisenberg 1/2 spin chain. The important point of this approach is the solution of the inverse quantum problem given by the XXZ spin chain. This solution as well as a simple formulae for the scalar product of the Bethe states, have enabled us to get the most basic correlation functions under the form of multiple integrals. The formalism of multiple integrals open the way for asymptotic analysis for a few physical quantities like the probability of vacuum formation. It is worth noticing that this formalism can give exact results for two-point functions that are the most important correlation functions for applications. A relationship has been discovered between these multiple integrals and the sum of the form factors. The results have been extended to dynamical correlation functions. (A.C.)

Full Text Available We prove the feasibility of evaluation of mitochondrial electron transport chainfunction in isolated mitochondria of smooth muscle cells of rats from uterus using fluorescence of NADH and FAD coenzymes. We found the inversely directed changes in FAD and NADH fluorescence intensity under normal functioning of mitochondrial electron transport chain. The targeted effect of inhibitors of complex I, III and IV changed fluorescence of adenine nucleotides. Rotenone (5 μM induced rapid increase in NADH fluorescence due to inhibition of complex I, without changing in dynamics of FAD fluorescence increase. Antimycin A, a complex III inhibitor, in concentration of 1 μg/ml caused sharp increase in NADH fluorescence and moderate increase in FAD fluorescence in comparison to control. NaN3 (5 mM, a complex IV inhibitor, and CCCP (10 μM, a protonophore, caused decrease in NADH and FAD fluorescence. Moreover, all the inhibitors caused mitochondria swelling. NO donors, e.g. 0.1 mM sodium nitroprusside and sodium nitrite similarly to the effects of sodium azide. Energy-dependent Ca2+ accumulation in mitochondrial matrix (in presence of oxidation substrates and Mg-ATP2- complex is associated with pronounced drop in NADH and FAD fluorescence followed by increased fluorescence of adenine nucleotides, which may be primarily due to Ca2+-dependent activation of dehydrogenases of citric acid cycle. Therefore, the fluorescent signal of FAD and NADH indicates changes in oxidation state of these nucleotides in isolated mitochondria, which may be used to assay the potential of effectors of electron transport chain.

Using the Feynman's path integral with topological constraints arising from the presence of one singular line, we find the homotopic probability distribution PnL for the winding number n and the partition function PL of the entangled system around a ribbon segment chain. We find that when the width of the ribbon segment chain 2a increases,the partition function exponentially decreases, whereas the free energy increases an amount, which is proportional to the square of the width. When the width tends to zero we obtain the same results as those of a single chain with one singular point.

We examined the link between household chaos (i.e., noise, clutter, disarray, lack of routines) and maternal executive function (i.e., effortful regulation of attention and memory), and whether it varied as a function of socioeconomic risk (i.e., single parenthood, lower mother and father educational attainment, housing situation, and father unemployment). We hypothesized that: 1) higher levels of household chaos would be linked with poorer maternal executive function, even when controlling for other measures of cognitive functioning (e.g., verbal ability), and 2) this link would be strongest in the most socioeconomically distressed or lowest-socioeconomic status households. The diverse sample included 153 mothers from urban and rural areas who completed a questionnaire and a battery of cognitive executive function tasks and a verbal ability task in the laboratory. Results were mixed for hypothesis 1, and consistent with hypothesis 2. Two-thirds of the variance overlapped between household chaos and maternal executive function, but only in families with high levels of socioeconomic risk. This pattern was not found for chaos and maternal verbal ability, suggesting that the potentially deleterious effects of household chaos may be specific to maternal executive function. The findings implicate household chaos as a powerful statistical predictor of maternal executive function in socioeconomically distressed contexts. PMID:22563703

Full Text Available Supply chain management represents new business philosophy and includes strategically positioned and much wider scope of activity in comparison with its "older brother" - management of logistics. Philosophy of the concept of supply chain is directed to more coordination of key business functions of every link in distribution chain in the process of organization of the flow of both goods and information, while logistic managing instruments are focused on internal optimum of flows of goods and information within one company. Applying the concept of integrated supply chain among several companies makes the importance of operative logistics activity even greater on the level of one company, thus advancing processes of optimum and coordination within and between different companies and confirms the importance of logistics performances for the company’s profitability. Besides the fact that the borders between companies are being deleted, this concept of supply chain in one distribution channel influences increasing of importance of functional, i.e. traditional business managing approaches but instead it points out the importance of process managing approaches. Although the author is aware that "there is nothing harder, more dangerous and with uncertain success, but to find a way for introducing some novelties (Machiavelli, it would be even his additional stimulation for trying to bring closer the concept and goals of supply chain implementation that are identified in key, relevant, modern, theoretical and consulting approaches in order to achieve better understanding of the subject and faster implementation of the concept of supply chain management by domestic companies.

Teleseismic receiver functions contain information regarding Earth structure beneath a seismic station. P-to-SV converted phases are often used to characterize crustal and upper-mantle discontinuities and isotropic velocity structures. More recently, P-to-SH converted energy has been used to interrogate the orientation of anisotropy at depth, as well as the geometry of dipping interfaces. Many studies use a trial-and-error forward modeling approach for the interpretation of receiver functions, generating synthetic receiver functions from a user-defined input model of Earth structure and amending this model until it matches major features in the actual data. While often successful, such an approach makes it impossible to explore model space in a systematic and robust manner, which is especially important given that solutions are likely non-unique. Here, we present a Markov chain Monte Carlo algorithm with Gibbs sampling for the interpretation of anisotropic receiver functions. Synthetic examples are used to test the viability of the algorithm, suggesting that it works well for models with a reasonable number of free parameters (function data, while others are subject to severe trade-offs-an important implication for studies that attempt to interpret Earth structure based on receiver function data. Finally, we apply our algorithm to receiver function data from station WCI in the central United States. We find evidence for a change in anisotropic structure at mid-lithospheric depths, consistent with previous work that used a grid search approach to model receiver function data at this station. Forward modeling of receiver functions using model space search algorithms, such as the one presented here, provide a meaningful framework for interrogating Earth structure from receiver function data.

Fibroblasts null for the transmembrane proteoglycan, syndecan-4, have an altered actin cytoskeleton, compared to matching wild-type cells. They do not organize alpha-smooth muscle actin into bundles, but will do so when full length syndecan-4 is re-expressed. This requires the central V region of......-smooth muscle actin organization, being reduced where syndecan-4 function was compromised by a lack of multiple heparan sulfate chains.......Fibroblasts null for the transmembrane proteoglycan, syndecan-4, have an altered actin cytoskeleton, compared to matching wild-type cells. They do not organize alpha-smooth muscle actin into bundles, but will do so when full length syndecan-4 is re-expressed. This requires the central V region......, clustering of one-chain syndecan-4 forms with antibodies overcame the block, indicating that valency of interactions with ligands is a key component of syndecan-4 function. Measurements of focal contact/adhesion size and focal adhesion kinase phosphorylation correlated with syndecan-4 status and alpha...

The gene encoding the gamma chain of the lymphocyte receptor for IL-2 lies in human X13.1 and is mutated in males with X-linked severe combined immunodeficiency (SCID). 27 X-linked SCID mutations have been found in our laboratory. Single strand conformation polymorphism (SSCP) analysis of genomic DNA using primers flanking each of the 8 exons was followed by direct sequencing of abnormally migrating fragments from SCID patients and family members. A 9 bp in-frame duplication insertion was found in IL2RG exon 5 of a patient from a large X-linked SCID pedigree; the resulting duplication of 3 extracellular amino acids, including the first tryptophan of the {open_quotes}WSXWS{close_quotes} cytokine binding motif, is predicted to disrupt interaction of the cytokine receptor chain with its ligand. Genetic linkage studies demonstrated that the grandmaternal X chromosome associated with SCID was contributed to 3 daughters, 2 obligate carriers and 1 woman of unknown status. However, this grandmother`s genomic DNA did not contain the insertion mutation, nor did she have skewed X-chromosome inactivation in her lymphocytes. That both obligate carrier daughters, but not the third daughter, had the insertion proved the grandmother to be a germline mosaic. A second proband had X-linked SCID with a branch point mutation due to substitution of T for A 15 bp 5{prime} of the start of IL2RG exon 3. This mutation resulted in undetectable IL2RG mRNA by Northern blot. Linkage analysis and sequencing of IL2RG DNA in this family proved the mutation to have originated in the germline of the proband`s grandfather, an immunocompetent individual who contributed an X chromosome with normal IL2RG to one daughter and a mutated X to the another.

We develop a general density functional theory for polyatomic molecules by taking the complete association limit of Wertheim's thermodynamic perturbation theory in a general way. By enforcing the complete association limit at an early point in the derivation and introducing the concept of molecular graphs, a general form for the free energy functional and segment densities are developed for both rigid and semiflexible molecules. The theory is applicable to branched chains, rings, or any other molecular structure. As an example the theory is applied as a second order perturbation theory to the case of molecules with a rigid three segment head and a fully flexible tail in a slit pore where bond angle of the rigid portion is an independent variable.

Full Text Available Mutations in GJA5 encoding the gap junction protein connexin40 (Cx40 have been linked to lone atrial fibrillation. Some of these mutants result in impaired gap junction function due to either abnormal connexin localization or impaired gap junction channels, which may play a role in promoting atrial fibrillation. However, the effects of the atrial fibrillation-linked Cx40 mutants on hemichannel function have not been studied. Here we investigated two atrial fibrillation-linked germline Cx40 mutants, V85I and L221I. These two mutants formed putative gap junction plaques at cell-cell interfaces, with similar gap junction coupling conductance as that of wild-type Cx40. Connexin deficient HeLa cells expressing either one of these two mutants displayed prominent propidium iodide-uptake distinct from cells expressing wild-type Cx40 or other atrial fibrillation-linked Cx40 mutants, I75F, L229M, and Q49X. Propidium iodide-uptake was sensitive to [Ca2+]o and the hemichannel blockers, carbenoxolone, flufenamic acid and mefloquine, but was not affected by the pannexin 1 channel blocking agent, probenecid, indicating that uptake is most likely mediated via connexin hemichannels. A gain-of-hemichannel function in these two atrial fibrillation-linked Cx40 mutants may provide a novel mechanism underlying the etiology of atrial fibrillation.

Full Text Available Abstract Background Development of effective scoring functions is a critical component to the success of protein structure modeling. Previously, many efforts have been dedicated to the development of scoring functions. Despite these efforts, development of an effective scoring function that can achieve both good accuracy and fast speed still presents a grand challenge. Results Based on a coarse-grained representation of a protein structure by using only four main-chain atoms: N, Cα, C and O, we develop a knowledge-based scoring function, called NCACO-score, that integrates different structural information to rapidly model protein structure from sequence. In testing on the Decoys'R'Us sets, we found that NCACO-score can effectively recognize native conformers from their decoys. Furthermore, we demonstrate that NCACO-score can effectively guide fragment assembly for protein structure prediction, which has achieved a good performance in building the structure models for hard targets from CASP8 in terms of both accuracy and speed. Conclusions Although NCACO-score is developed based on a coarse-grained model, it is able to discriminate native conformers from decoy conformers with high accuracy. NCACO is a very effective scoring function for structure modeling.

We studied the presence of zinc tolerance in enchytraeid worm (Cognettia sphagnetorum, Oligochaeta) from a metal-polluted forest soil in The Netherlands. In a dose response experiment, we compared Zn sensitivity, measured as body growth and reproduction, of these enchytraeids with that of animals taken from three unpolluted sites. Because C. sphagnetorum is a keystone species, regulating microbial processes in coniferous forest soil, we performed a microcosm experiment to study the interaction of enchytraeids from several sites with soil microbes. The idea was to study whether there is a link between metal stress response of individuals (tolerance level, life history alteration) and changes observed at higher organization levels of the biological system (trophic interaction and decomposition processes). We did not find evidence for increased metal tolerance of C. sphagnetorum. Worms from the polluted site actually had reduced body growth, indicating negative fitness effects caused by long-lasting metal stress. The density and biomass of the worm population from the polluted site was low in Zn contaminated soil. Presence of enchytraeids enhanced and Zn contamination reduced the activity of microbes in the soil. Enchytraeids from different sites with different life histories and population development, however, had the same effect on microbes. Hence, observed stress responses of individuals and populations could not be linked to density-dependent trophic interactions and ecosystem functioning in the soil-decomposer food chain.

With accelerating the comprehensive development of modem military logistics, establishing the civil - military on modem military logistics system is the inevitable trend, which relies on the national logistics system and social resource security. This paper brought forward to establish double chain - link structure of military logistics system. Based on the analy- sis of military logistics current situation and characteristic, expounded the meaning of establishing double chain - link structure military logistics system, analyzed the mainly problem of this system under the current situation, and provided some countermeasures for it.%在全面建设现代后勤的大背景下，依托国家物流体系和社会保障资源，构建军民结合的现代军事物流体系是大势所趋。提出了构建双链式军事物流体系的理念，在分析体系内涵和特征的基础上，阐述了构建体系的必要性，着重剖析了当前条件下体系构建面临的主要问题，并有针对性地给出对策建议。

GeoChip is a comprehensive functional gene array that targets key functional genes involved in the geochemical cycling of N, C, and P, sulfate reduction, metal resistance and reduction, and contaminant degradation. Studies have shown the GeoChip to be a sensitive, specific, and high-throughput tool for microbial community analysis that has the power to link geochemical processes with microbial community structure. However, several challenges remain regarding the development and applications of microarrays for microbial community analysis.

Surface active amide-functionalized ionic liquids (ILs) consisting of a long alkyl chain (C6C14) connected to a polar head group (methylimidazolium or pyridinium cation) via an amide functional group were synthesized and their thermal stability, micellar properties and antimicrobial activity in aqueous solution investigated. The incorporation of an amide group increased the thermal stability of the functionalized ionic liquids compared to simple alkyl chain substituted ionic liquids. The surface activity and aggregation behaviour in aqueous solution of amide-functionalized ionic liquids were examined by tensiometry, conductivity and spectrofluorimetry. Amide-functionalized ILs displayed surface activity and their critical micelle concentration (cmc) in aqueous media decreased with the elongation of the alkyl side chain as occurs for typical surfactants. Compared to non-functionalized ILs bearing the same alkyl chain, ionic liquids with an amide moiety possess higher surface activity (pC20) and lower cmc values. The introduction of an amide group in the hydrophobic chain close to the polar head enhances adsorption at the air/water interface and micellization which could be attributed to the H-bonding in the headgroup region. The antimicrobial activity was evaluated against a panel of representative Gram-negative and Gram-positive bacteria and fungi. Amide-functionalized ILs with more than eight carbon atoms in the side chain showed broad antimicrobial activity. Antibacterial activities were found to increase with the alkyl chain length being the C12 homologous the most effective antimicrobial agents. The introduction of an amide group enhanced significantly the antifungal activity as compared to non-functionalized ILs.

To add novel functionality to quantum dots (QDs), we synthesized water-soluble and pH-responsive block-type polymers by reversible addition-fragmentation chain transfer (RAFT) polymerization. The polymers were composed of cytocompatible 2-methacryloyloxyethyl phosphorylcholine (MPC) polymer segments, which contain a small fraction of active ester groups and can be used to conjugate biologically active compounds to the polymer, and pH-responsive poly(2-(N,N-diethylamino) ethyl methacrylate (DEAEMA)) segments. One terminal of the polymer chain had a hydrophobic alkyl group that originated from the RAFT initiator. This hydrophobic group can bind to the hydrophobic layer on the QD surface. A fluorescent dye was conjugated to the polymer chains via the active ester group. The block-type polymers have an amphiphilic nature in aqueous medium. The polymers were thus easily bound to the QD surface upon evaporation of the solvent from a solution containing the block-type polymer and QDs, yielding QD/fluorescence dye-conjugated polymer hybrid nanoparticles. Fluorescence resonance energy transfer (FRET) between the QDs (donors) and the fluorescent dye molecules (acceptors) was used to obtain information on the conformational dynamics of the immobilized polymers. Higher FRET efficiency of the QD/fluorescent dye-conjugated polymer hybrid nanoparticles was observed at pH 7.4 as compared to pH 5.0 due to a stretching-shrinking conformational motion of the poly(DEAEMA) segments in response to changes in pH. We concluded that the block-type MPC polymer-modified nanoparticles could be used to evaluate the pH of cells via FRET fluorescence based on the cytocompatibility of the MPC polymer.

Herceptin/Trastuzumab is a humanized IgG1κ light chain antibody used to treat some forms of breast cancer. A phage-displayed recombinant antibody library was used to obtain a single chain fragment variable (scFv, designated 2B4) to a linear synthetic peptide representing Herceptin's heavy chain CDR3. Enzyme linked immunosorbent assays (ELISAs) and piezoimmunosensor/quartz crystal microbalance (QCM) assays were used to characterize 2B4-binding activity to both native and heat denatured Herceptin. The 2B4 scFv specifically bound to heat denatured Herceptin in a concentration dependent manner over a wide (35-220.5 nM) dynamic range. Herceptin denatures and forms significant amounts of aggregates when heated. UV-vis characterization confirms that Herceptin forms aggregates as the temperature used to heat Herceptin increases. QCM affinity assay shows that binding stoichiometry between 2B4 scFv and Herceptin follows a 1:2 relationship proving that 2B4 scFv binds strongly to the dimers of heat denatured Herceptin aggregates and exhibits an affinity constant of 7.17 × 10(13) M(-2). The 2B4-based QCM assay was more sensitive than the corresponding ELISA. Combining QCM with ELISA can be used to more fully characterize nonspecific binding events in assays. The potential theoretical and clinical implications of these results and the advantages of the use of QCM to characterize human therapeutic antibodies in samples are also discussed.

Full Text Available Iron is an essential micronutrient that plays important roles as a redox cofactor in a variety of processes, many of which are related to DNA metabolism. The E2 ubiquitin conjugase UBC13, the only E2 protein that is capable of catalyzing the formation of noncanonical K63-linked ubiquitin chains, has been associated with the DNA damage tolerance pathway in eukaryotes, critical for maintenance of genome stability and integrity. We previously showed that UBC13 and an interacting E3 ubiquitin ligase, RGLG, affect the differentiation of root epidermal cells in Arabidopsis. When grown on iron-free media, Arabidopsis plants develops root hairs that are branched at their base, a response that has been interpreted as an adaption to reduced iron availability. Mutations in UBC13A abolished the branched root hair phenotype. Unexpectedly, mutations in RGLG genes caused constitutive root hair branching. Based on recent results that link endocytotic turnover of plasma membrane-bound PIN transporters to K63-linked ubiquitination, we reinterpreted our results in a context that classifies the root hair phenotype of iron-deficient plants as a consequence of altered auxin distribution. We show here that UBC13A/B and RGLG1/2 are involved in DNA damage repair and hypothesize that UBC13 protein becomes limited under iron-deficient conditions to prioritize DNA metabolism. The data suggest that genes involved in combating detrimental effects on genome stability may represent essential components in the plant’s stress response.

Complement C1q is a soluble pattern recognition molecule comprising six heterotrimeric subunits assembled from three polypeptide chains (A-C). Each heterotrimer forms a collagen-like stem prolonged by a globular recognition domain. These recognition domains sense a wide variety of ligands, including pathogens and altered-self components. Ligand recognition is either direct or mediated by immunoglobulins or pentraxins. Multivalent binding of C1q to its targets triggers immune effector mechanisms mediated via its collagen-like stems. The induced immune response includes activation of the classical complement pathway and enhancement of the phagocytosis of the recognized target. We report here, the first production of a single-chain recombinant form of human C1q globular region (C1q-scGR). The three monomers have been linked in tandem to generate a single continuous polypeptide, based on a strategy previously used for adiponectin, a protein structurally related to C1q. The resulting C1q-scGR protein was produced at high yield in stably transfected 293-F mammalian cells. Recombinant C1q-scGR was correctly folded, as demonstrated by its X-ray crystal structure solved at a resolution of 1.35 Å. Its interaction properties were assessed by surface plasmon resonance analysis using the following physiological C1q ligands: the receptor for C1q globular heads, the long pentraxin PTX3, calreticulin, and heparin. The 3D structure and the binding properties of C1q-scGR were similar to those of the three-chain fragment generated by collagenase digestion of serum-derived C1q. Comparison of the interaction properties of the fragments with those of native C1q provided insights into the avidity component associated with the hexameric assembly of C1q. The interest of this functional recombinant form of the recognition domains of C1q in basic research and its potential biomedical applications are discussed.

Full Text Available Inborn errors of metabolism (IEMs occur with high incidence in human populations. Especially prevalent among these are inborn deficiencies in fatty acid β-oxidation (FAO, which are clinically associated with developmental neuropsychiatric disorders, including autism. We now report that neural stem cell (NSC-autonomous insufficiencies in the activity of TMLHE (an autism risk factor that supports long-chain FAO by catalyzing carnitine biosynthesis, of CPT1A (an enzyme required for long-chain FAO transport into mitochondria, or of fatty acid mobilization from lipid droplets reduced NSC pools in the mouse embryonic neocortex. Lineage tracing experiments demonstrated that reduced flux through the FAO pathway potentiated NSC symmetric differentiating divisions at the expense of self-renewing stem cell division modes. The collective data reveal a key role for FAO in controlling NSC-to-IPC transition in the mammalian embryonic brain and suggest NSC self renewal as a cellular mechanism underlying the association between IEMs and autism.

Full Text Available Elongation of Very Long chain fatty acids-like 4 (ELOVL4 is a fatty acid elongase responsible for the biosynthesis of very long chain (VLC; ≥ C26 fatty acids in the retina, brain, skin, Meibomian gland, and testes. Heterozygous inheritance of mutant ELOVL4 causes juvenile macular degeneration in autosomal dominant Stargardt-like macular dystrophy (STGD3. Retinal photoreceptors are enriched with VLC polyunsaturated fatty acids (VLC-PUFAs, which have been shown by our group and others to be necessary for the survival of rod photoreceptors. Our group performed a series of studies using mice conditionally depleted of retinal Elovl4 (KO aimed at understanding the role of VLC-PUFAs in long-term retinal health and function, focusing on the role of these fatty acids in mediating synaptic function between the photoreceptors and the rest of the neural retina. The absence of VLC-PUFA from the retina of KO mice resulted in a marked decrease in retinal b-wave responses of the electroretinogram as well as a decrease in the amplitude of the oscillatory potentials mediated by the neural retina. Although there were no measureable differences between KO and wild type (WT mice in either pre-synaptic rod calcium channel function or post-synaptic bipolar cell glutamate receptor responses, ultrastructural analysis revealed a marked decrease in the diameter of synaptic vesicles in rod terminals. Recent quantification suggests that this decrease in synaptic vesicle size due to the absence of VLC-PUFAs in KO mice, and the consequent decrease in glutamate content, could account for the decrease in b-wave response amplitudes that were previously measured in these animals.

Full Text Available The present paper is focused on the study of those relations that auxiliary verbs can establish among themselves when chained in a sequence. Regarding those sequences, which in Spanish can be considerably long, the literature has displayed primarily interest in formulating a set of principles that can predict possible relative orderings among auxiliaries. On the contrary, our paper delves into a less walked path: the description of relations established within an auxiliary chain. We will start from the traditional definition of auxiliary verb as a unit that modifies the ‘main’ or ‘lexical’ verb, and proceed to show that such a conception makes the wrong predictions when it comes to explain those internal relations, for it only accounts for a subset of the cases. This explanatory problem is common to both traditional and more formal models. In our opinion, the distinction between between lexical and functional auxiliaries that we propose in this work, in the context of a dynamic computational model that includes and derives this distinction, allows us to overcome these shortcomings of traditional analyses.

Generalized linear models (GLM) with a canonical logit linkfunction are the primary modeling technique used to relate a binary outcome to predictor variables. However, noncanonical links can offer more flexibility, producing convenient analytical quantities (e.g., probit GLMs in toxicology) and desired measures of effect (e.g., relative risk from log GLMs). Many summary goodness-of-fit (GOF) statistics exist for logistic GLM. Their properties make the development of GOF statistics relatively straightforward, but it can be more difficult under noncanonical links. Although GOF tests for logistic GLM with continuous covariates (GLMCC) have been applied to GLMCCs with log links, we know of no GOF tests in the literature specifically developed for GLMCCs that can be applied regardless of linkfunction chosen. We generalize the Tsiatis GOF statistic originally developed for logistic GLMCCs, (TG), so that it can be applied under any linkfunction. Further, we show that the algebraically related Hosmer-Lemeshow (HL) and Pigeon-Heyse (J(2) ) statistics can be applied directly. In a simulation study, TG, HL, and J(2) were used to evaluate the fit of probit, log-log, complementary log-log, and log models, all calculated with a common grouping method. The TG statistic consistently maintained Type I error rates, while those of HL and J(2) were often lower than expected if terms with little influence were included. Generally, the statistics had similar power to detect an incorrect model. An exception occurred when a log GLMCC was incorrectly fit to data generated from a logistic GLMCC. In this case, TG had more power than HL or J(2) .

To date, the major dilemma concerning frailty is the lack of a standardized language regarding its operationalization. Considering the demographic challenge that the world is facing, standardization of frailty identification is indeed the first step in tackling the burdensome consequences of frailty. To demonstrate this diversity in frailty assessment, the available frailty instruments have been linked to the International Classification of Functioning, Disability, and Health (ICF): a standardized and hierarchically coded language developed by World Health Organization regarding health conditions and their positive (functioning) and negative (disability) consequences. A systematic review on frailty instruments was carried out in PubMed, Web of Knowledge, and PsycINFO. The items of the identified frailty instruments were then linked to the ICF codes. 79 original or adapted frailty instruments were identified and categorized into single (n = 25) and multidomain (n = 54) groups. Only 5 frailty instruments (indexes) were linked to all 5 ICF components. Whereas the ICF components Body Functions and Activities and Participation were frequently linked to the frailty instruments, Body Structures, Environmental and Personal factors were sparingly represented mainly in the multidomain frailty instruments. This review highlights the heterogeneity in frailty operationalization. Environmental and personal factors should be given more thought in future frailty assessments. Being unambiguous, structured, and neutral, the ICF language allows comparing observations made with different frailty instruments. In conclusion, this systematic overview and ICF translation can be a cornerstone for future standardization of frailty assessment.

We examined the long-term effect of feeding coconut oil (CO; rich in lauric acid, C12) on voluntary food intake and nutrient utilisation in rainbow trout (Oncorhynchus mykiss), with particular attention to the metabolic use (storage or oxidation) of ingested medium-chain TAG. Trout were fed for 15 weeks one of the four isoproteic diets containing fish oil (FO) or CO as fat source (FS), incorporated at 5% (low fat, LF) or 15% (high fat, HF). Fat level or FS did not modify food intake (g/kg(0·8) per d), despite higher intestinal cholecystokinin-T mRNA in trout fed the HF-FO diet. The HF diets relative to the LF ones induced higher growth and adiposity, whereas the replacements of FO by CO resulted in similar growth and adiposity. This, together with the substantial retention of C12 (57% of intake), suggests the relatively low oxidation of ingested C12. The down-regulation of carnitine palmitoyl-transferase-1 (CPT-1) confirms the minor dependency of medium-chain fatty acids (MCFA) on CPT-1 to enter the mitochondria. However, MCFA did not up-regulate mitochondrial oxidation evaluated using hepatic hydroxyacyl-CoA dehydrogenase as a marker, in line with their high retention in body lipids. At a low lipid level, MCFA increased mRNA levels of fatty acid synthase, elongase and stearoyl-CoA desaturase in liver, showing the hepatic activation of fatty acid synthesis pathways by MCFA, reflected by increased 16 : 0, 18 : 0, 16 : 1, 18 : 1 body levels. The high capacity of trout to incorporate and transform C12, rather than to readily oxidise C12, contrasts with data in mammals and may explain the absence of a satiating effect of CO in rainbow trout.

The electronic structures of self-assembled hybrid chains comprising Ag atoms and organic molecules were studied using scanning tunneling microscopy (STM) and spectroscopy (STS) in parallel with density functional theory (DFT). Hybrid chains were prepared by catalytic breaking of Br-C bonds in 4,4″-dibromo-p-terphenyl molecules, followed by spontaneous formation of Ag-C bonds on Ag(111). An atomic model was proposed for the observed hybrid chain structures. Four electronic states were resolved using STS measurements, and strong energy dependence was observed in STM images. These results were explained using first-principles calculations based on DFT.

Cytoplasmic dynein 1 (dynein) is a minus end-directed microtubule motor protein with many cellular functions, including during cell division. The role of the light intermediate chains (LICs; DYNC1LI1 and 2) within the complex is poorly understood. In this paper, we have used small interfering RNAs or morpholino oligonucleotides to deplete the LICs in human cell lines and Xenopus laevis early embryos to dissect the LICs' role in cell division. We show that although dynein lacking LICs drives microtubule gliding at normal rates, the LICs are required for the formation and maintenance of a bipolar spindle. Multipolar spindles with poles that contain single centrioles were formed in cells lacking LICs, indicating that they are needed for maintaining centrosome integrity. The formation of multipolar spindles via centrosome splitting after LIC depletion could be rescued by inhibiting Eg5. This suggests a novel role for the dynein complex, counteracted by Eg5, in the maintenance of centriole cohesion during mitosis.

Dung beetles form an insect group that fulfils important functions in terrestrial ecosystems throughout the world. These include nutrient cycling through dung removal, soil bioturbation, plant growth, secondary seed dispersal and parasite control. We conducted field experiments at two sites in the northern hemisphere temperate region in which dung removal and secondary seed dispersal were assessed. Dung beetles were classified in three functional groups, depending on their size and dung manipulation method: dwellers, large and small tunnelers. Other soil inhabiting fauna were included as a fourth functional group. Dung removal and seed dispersal by each individual functional group and combinations thereof were estimated in exclusion experiments using different dung types. Dwellers were the most diverse and abundant group, but tunnelers were dominant in terms of biomass. All dung beetle functional groups had a clear preference for fresh dung. The ecosystem services in dung removal and secondary seed dispersal provided by dung beetles were significant and differed between functional groups. Although in absolute numbers more dwellers were found, large tunnelers were disproportionally important for dung burial and seed removal. In the absence of dung beetles, other soil inhabiting fauna, such as earthworms, partly took over the dung decomposing role of dung beetles while most dung was processed when all native functional groups were present. Our results, therefore, emphasize the need to conserve functionally complete dung ecosystems to maintain full ecosystem functioning.

Objective To study the effect of 4- 6 weeks' treadmill training of male SD rats on the contractile function of their gnstroenemius myosin heavy chain (MHC). Methods Forty male SD rats were randomly divided into control group and training group. The treadmill training of the training group rats was incessantly performed for 4- 6 weeks at an intensity of about 75% VO2max (18. 5- 24 m/min, gradient of 0°, each training session lasting 50 minutes, twice a day). The content of gastrocnemlas MHC mRNA was tested by reverse transcription polymernse chain reaction (RT-PCR), and the changes of muscle fibre and its cross-section area (CSA) were measured using immunohistochemistry. Electric stimulation tests were used to determine the maximal tension of isometric contraction of the post-training gastrocnemius. Results ① After continuous treadmill training for 4 - 6 weeks, we found that the content of the total MHC, MHC Ⅰ , MHC Ⅱ x, MHC Ⅱ a mRNAs was 105%, 105%, 109% and 108% of that in the resting control group, respectively, and the MHC Ⅱ b mRNA content did not change significantly. The percentage of MHC Ⅰ mRNA in the total MHC mRNA increased while that of MHC Ⅱ mRNA decreased after aerobic training. ② The slow type of fibre type Ⅰ was the main part of the MHC after training and the CSA of the muscle fibres increased simultaneously. ③ The maximal tension of isometric contraction by pulse stimulation of square wave in the training group increased significantly compared with that in the control group (P<0. 01). Conclusion The findings indicate that aerobic exercise may promote an increase in the contractile function of MHC.

This article introduces the systems-centered concept of the "group mind" by linking systems-centered thinking and interpersonal neurobiology, building on Siegel's definition of mind as the process of regulating the flow of energy and information. Functional subgrouping, the systems-centered group method for resolving conflicts, discriminates and integrates the flow of energy and information within and between group members, subgroups, and the group-as-a-whole, thus potentiating survival, development, and transformation. This article uses the interpersonal neurobiological framework to discuss functional subgrouping as a tool for developing the group mind: considering how functional subgrouping facilitates emotional regulation, creates a secure relational context, and potentiates neural integration.

Short-chain fatty acids (SCFA), fermentation products of fiber, are believed to play a role in intestinal adaptation. Although the administration of fiber or the infusion of SCFA has been shown to cause colonic growth, studies have been done primarily in enterally fed animals. In addition, the effects of SCFA on absorptive function have not been determined. Adult male rats were maintained on total parenteral nutrition (TPN) and, in addition, received either 150 mmol/L of saline or 150 mmol/L of SCFA mixture (60:25:15, acetate:propionate:butyrate) into the proximal colon. One week later, the in vivo absorption of water, electrolytes, and 20 mmol/L of butyrate was measured. After the rats were killed, parameters of colonic mass were determined. SCFA infusion into the colon had no significant effect on absorptive function. However, significantly greater mucosal height (p less than .01) and mucosal DNA (p less than .05), were observed. Although SCFA has a modest effect on colonic structure, they do not influence absorptive function in TPN rats.

The efficiency of polymer - metal oxide hybrid solar cells depends critically on the intimacy of mixing of the two semiconductors. The effect of side chainfunctionalization on the morphology and performance of conjugated polymer:ZnO solar cells is investigated. Using an ester-functionalized side ch

In this article, the authors evaluated functional communication training (FCT) and a chained schedule of reinforcement for the treatment of challenging behavior exhibited by two individuals diagnosed with Asperger syndrome and autism, respectively. Following a functional analysis with undifferentiated results, the authors demonstrated that…

Waste management in construction is critical for the sustainable treatment of building-related construction and demolition (C&D) waste materials, and recycling of these wastes has been considered as one of the best strategies in minimization of C&D debris. However, recycling of C&D materials may not always be a feasible strategy for every waste type and therefore recycling and other waste treatment strategies should be supported by robust decision-making models. With the aim of assessing the net carbon, energy, and water footprints of C&D recycling and other waste management alternatives, a comprehensive economic input-output-based hybrid life-cycle assessment model is developed by tracing all of the economy-wide supply-chain impacts of three waste management strategies: recycling, landfilling, and incineration. Analysis results showed that only the recycling of construction materials provided positive environmental footprint savings in terms of carbon, energy, and water footprints. Incineration is a better option as a secondary strategy after recycling for water and energy footprint categories, whereas landfilling is found to be as slightly better strategy when carbon footprint is considered as the main focus of comparison. In terms of construction materials' environmental footprint, nonferrous metals are found to have a significant environmental footprint reduction potential if recycled.

The one-dimensional falling motion of a bungee chain suspended from a rigid support and of a chain falling from a resting heap on a table is studied. Their Lagrangians are found to contain no explicit time dependence. As a result, these falling chains are conservative systems. Each of their Lagrange's equations of motion is shown to contain a term that enforces energy conservation when masses are transferred between subchains. We show in particular that Cayley's 1857 energy nonconserving solution for a chain falling from a resting heap is incorrect because it neglects the energy gained when the transferred link is emitted by the emitting subchain. The maximum chain tension measured by Calkin and March for the falling bungee chain is given a simple if rough interpretation. In the simplified one-dimensional treatment, the kinetic energy of the center of mass of the falling bungee chain is found to be converted by the chain tension at the rigid support into the internal kinetic energy of the chain. However, as t...

Maintenance of organ homeostasis and control of appropriate response to environmental alterations requires intimate coordination of cellular function and tissue organization. An important component of this coordination may be provided by proteins that can serve distinct, but linked, functions on both sides of the plasma membrane. Here we present a novel hypothesis in which non-classical secretion can provide a mechanism through which single proteins can integrate complex tissue functions. Single genes can exert a complex, dynamic influence through a number of different processes that act to multiply the function of the gene product(s). Alternative splicing can create many different transcripts that encode proteins of diverse, even antagonistic, function from a single gene. Posttranslational modifications can alter the stability, activity, localization, and even basic function of proteins. A protein can exist in different subcellular localizations. More recently, it has become clear that single proteins can function both inside and outside the cell. These proteins often lack defined secretory signal sequences, and transit the plasma membrane by mechanisms separate from the classical ER/Golgi secretory process. When examples of such proteins are examined individually, the multifunctionality and lack of a signal sequence are puzzling - why should a protein with a well known function in one context function in such a distinct fashion in another? We propose that one reason for a single protein to perform intracellular and extracellular roles is to coordinate organization and maintenance of a global tissue function. Here, we describe in detail three specific examples of proteins that act in this fashion, outlining their specific functions in the extracellular space and in the intracellular space, and we discuss how these functions may be linked. We present epimorphin/syntaxin-2, which may coordinate morphogenesis of secretory organs (as epimorphin) with control of

Full Text Available Mammalian spermatogenesis is a highly regulated multistage process of sperm generation. It is hard to uncover the real function of a testis specific gene in vitro since the in vitro model is not yet mature. With the development of the CRISPR/Cas9 (Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR-associated 9 system, we can now rapidly generate knockout mouse models of testis specific genes to study the process of spermatogenesis in vivo. SYCP3-like X-linked 2 (SLX2 is a germ cell specific component, which contains a Cor1 domain and belongs to the XLR (X-linked, lymphocyte regulated family. Previous studies suggested that SLX2 might play an important role in mouse spermatogenesis based on its subcellular localization and interacting proteins. However, the function of SLX2 in vivo is still elusive. Here, to investigate the functions of SLX2 in spermatogenesis, we disrupted the Slx2 gene by using the CRISPR/Cas9 system. Since Slx2 is a testis specific X-linked gene, we obtained knockout male mice in the first generation and accelerated the study process. Compared with wild-type mice, Slx2 knockout mice have normal testis and epididymis. Histological observation of testes sections showed that Slx2 knockout affected none of the three main stages of spermatogenesis: mitosis, meiosis and spermiogenesis. In addition, we further confirmed that disruption of Slx2 did not affect the number of spermatogonial stem cells, meiosis progression or XY body formation by immunofluorescence analysis. As spermatogenesis was normal in Slx2 knockout mice, these mice were fertile. Taken together, we showed that Slx2 itself is not an essential gene for mouse spermatogenesis and CRISPR/Cas9 technique could speed up the functional study of testis specific X-linked gene in vivo.

Generic inhomogeneous integrable XXZ chains with arbitrary spins are studied by means of the quantum separation of variables (SOV) method. Within this framework, a complete description of the spectrum (eigenvalues and eigenstates) of the antiperiodic transfer matrix is derived in terms of discrete systems of equations involving the inhomogeneity parameters of the model. We show here that one can reformulate this discrete SOV characterization of the spectrum in terms of functional T-Q equations of Baxter's type, hence proving the completeness of the solutions to the associated systems of Bethe-type equations. More precisely, we consider here two such reformulations. The first one is given in terms of Q-solutions, in the form of trigonometric polynomials of a given degree $N_s$, of a one-parameter family of T-Q functional equations with an extra inhomogeneous term. The second one is given in terms of Q-solutions, again in the form of trigonometric polynomials of degree $N_s$ but with double period, of Baxter's ...

The α-KTx14 subfamily of scorpion toxins is a group of short-chain polypeptides affecting K(+) channels, including five known members which are restrictedly distributed in Mesobuthus martensii. Here, we describe seven new α-KTx14 peptides from M. martensii and its sibling species Mesobuthus eupeus, two of which (termed MarKTX-3 and MeuKTX-1) were chemically synthesized and refolded for structural and functional studies. Electrophysiological recordings of effects of these two peptides on an array of voltage-gated potassium channels revealed that MarKTX-3 was capable of inhibiting five mammalian K(v)1 isoforms (rK(v)1.1-rK(v)1.5) and the Drosophila Shaker channel with low potency whereas MeuKTX-1 lacks such activity. Circular dichroism spectroscopy analysis combined with homology modeling demonstrates that MarKTX-3 and MeuKTX-1 both adopt a similar cysteine-stabilized α-helical and β-sheet fold. Evolutionary analysis indicates accelerated amino acid substitutions in the mature-peptide-encoding regions of orthologous α-KTx14 peptides after speciation, thereby providing evidences for adaptive evolution and functional divergence of this subfamily.

It is widely known that branched chain amino acids (BCAA) are not only elementary components for building muscle tissue but also participate in increasing protein synthesis in animals and humans. BCAA (isoleucine, leucine and valine) regulate many key signaling pathways, the most classic of which is the activation of the mTOR signaling pathway. This signaling pathway connects many diverse physiological and metabolic roles. Recent years have witnessed many striking developments in determining the novel functions of BCAA including: (1) Insufficient or excessive levels of BCAA in the diet enhances lipolysis. (2) BCAA, especially isoleucine, play a major role in enhancing glucose consumption and utilization by up-regulating intestinal and muscular glucose transporters. (3) Supplementation of leucine in the diet enhances meat quality in finishing pigs. (4) BCAA are beneficial for mammary health, milk quality and embryo growth. (5) BCAA enhance intestinal development, intestinal amino acid transportation and mucin production. (6) BCAA participate in up-regulating innate and adaptive immune responses. In addition, abnormally elevated BCAA levels in the blood (decreased BCAA catabolism) are a good biomarker for the early detection of obesity, diabetes and other metabolic diseases. This review will provide some insights into these novel metabolic and physiological functions of BCAA.

Cytochrome b558/566 from the archaeon Sulfolobus acidocaldarius (DSM 639) has been described as a novel highly glycosylated membrane-bound b-type hemoprotein [Hettmann, T., Schmidt, C. L., Anemüller, S., Zähringer, U., Moll, H., Petersen, A. & Schäfer, G. (1998) J. Biol. Chem. 273, 12032-12040]. The purified cytochrome b558/566 was characterized by MALDI MS as a 64-kDa (glyco)protein expressing 17% glycosylation. Detailed chemical studies showed that it was exclusively O-mannosylated with monosaccharides and N-glycosylated with at least seven hexasaccharide units having the same unique structure. The hexasaccharide was released by cleavage with peptide:N-glycosidase (PNGase) F and found to consist of two residues each of Man and GlcNAc and one residue each of Glc and 6-deoxy-6-sulfoglucose (6-sulfoquinovose). The last sugar has been known as a component of glycolipids of plants and some prokaryotes, but has not been hitherto found in bacterial glycoproteins. Digestion with trypsin/pronase gave a mixture of glycopeptides with the same Asn-linked hexasaccharide chain, from which an N-glycosylated Tyr-Asn dipeptide was purified by gel chromatography and anion-exchange HPLC. Studies of the degradation products using methylation analysis, ESI MS, MALDI MS, and 1H and 13C NMR spectroscopy, including 1H,13C HMQC and NOESY experiments, established the structure of the unique Asn-linked hexasaccharide chain of cytochrome b558/566.

We report on a temperature-dependent resonance Raman spectral characterization of the polyene chain of canthaxanthin.It is observed that all vibrational intensities of the polyene chain are inversely proportional to temperature,which is analyzed by the resonance Raman effect and the coherent weakly damped electron/lattice vibrations.The increase in intensity of the CC overtone/combination relative to the fundamental with temperature decreasing is detected and discussed in terms of electron/phonon coupling and the activation energy Uop.Moreover,the polyene chain studies using the density functional theory B3LYP/6-31G* level reveal a prominent peak at 1525 cm-1 consisting of two closely spaced modes that are both dominated by C=C stretching coordinates of the polyene chain.

Full Text Available Sequenced physiologic muscle activations in the upper and lower extremity result in an integrated biomechanical task. This sequencing is known as the kinetic chain, and, in upper extremity dominant tasks, the energy development and output follows a proximal to distal sequencing. Impairment of one or more kinetic chainlinks can create dysfunctional biomechanical output leading to pain and/or injury. When deficits exist in the preceding links, they can negatively affect the shoulder. Rehabilitation of shoulder injuries should involve evaluation for and restoration of all kinetic chain deficits that may hinder kinetic chainfunction. Rehabilitation programs focused on eliminating kinetic chain deficits, and soreness should follow a proximal to distal rationale where lower extremity impairments are addressed in addition to the upper extremity impairments. A logical progression focusing on flexibility, strength, proprioception, and endurance with kinetic chain influence is recommended.

Sequenced physiologic muscle activations in the upper and lower extremity result in an integrated biomechanical task. This sequencing is known as the kinetic chain, and, in upper extremity dominant tasks, the energy development and output follows a proximal to distal sequencing. Impairment of one or more kinetic chainlinks can create dysfunctional biomechanical output leading to pain and/or injury. When deficits exist in the preceding links, they can negatively affect the shoulder. Rehabilitation of shoulder injuries should involve evaluation for and restoration of all kinetic chain deficits that may hinder kinetic chainfunction. Rehabilitation programs focused on eliminating kinetic chain deficits, and soreness should follow a proximal to distal rationale where lower extremity impairments are addressed in addition to the upper extremity impairments. A logical progression focusing on flexibility, strength, proprioception, and endurance with kinetic chain influence is recommended.

This paper describes the implementation and evaluation of a journal club in a privately funded palliative care unit. Journal club meetings were initiated as part of a quality improvement process to foster the uptake of evidence-based practice. Nurses were presented with research articles each month and discussions were conducted focussing on methodological considerations of the research and implications of the research for patient care. The maximum number of attendees at any one meeting was nine and the minimum number was four. Overall, evaluations were positive about all aspects of the meetings. Attendees found that the selected articles were relevant, providing new information, stimulated discussion and reflection on clinical practice and encouraged further reading. One of the positive aspects of the meetings identified by participants was the facilitation style that enabled discussion in a safe and supportive environment. An important outcome of the meetings is the potential to explore evidence-based practices relevant to palliative care and to implement new practices or revise existing ones. As part of this process practice changes and clinical guidelines have been implemented. A dedicated facilitator with university links and a supportive organisational culture promoted club meetings as a practical way to provide clinical nurses with the opportunity to explore evidence-based research in the area of palliative care.

Full Text Available Background: Perinatal viral infections of fetus are among the leading causes of congenital cataract and identifying the viral etiology is important. Objectives: To detect the presence of Rubella virus (RV, herpes simplex virus (HSV and cytomegalovirus (CMV in lens aspirate specimens obtained from patients with congenital cataract and relate the results with serology. Setting and Design: Prospective study carried out in tertiary care hospital. Materials and Methods: Fifty lens aspirates from 50 infants with congenital cataract were subjected to HSV, RV isolation and polymerase chain reaction (PCR for detection of HSV and CMV. Reverse transcription polymerase chain reaction (RT-PCR was applied for RV detection. Peripheral blood specimens were screened for anti-HSV, RV and CMV antibodies by enzyme-linked immunosorbant assay (ELISA. Results: Rubella virus was detected in nine (18% lens aspirates, by nRT-PCR which includes six positive by culture. HSV-2 DNA was detected in nine other lens aspirates, while CMV was not detected by PCR. Serological results did not correlate with the presence of viruses in the lens aspirates. This is the first report of detection of HSV-2 DNA in cases of congenital cataract. Conclusions: Cytomegalovirus may not be playing a significant role in causation of congenital cataract. The role of serology in identifying causative viral infection for congenital cataract needs to be re-evaluated.

Full Text Available The concept of the "keystone species" is redefined to allow for the a priori prediction of these species within ecosystems. A keystone species is held to be a strongly interacting species whose top-down effect on species diversity and competition is large relative to its biomass dominance within a functional group. This operational definition links the community importance of keystone species to a specific ecosystem process, e.g., the regulation of species diversity, within functional groups at lower trophic levels that are structured by competition for a limited resource. The a priori prediction of keystone species has applied value for the conservation of natural areas.

We have studied the impact of overexpression of an intracellular signaling protein, integrin-linked kinase (ILK), on the survival and function of encapsulated islet tissue used for the treatment of type 1 diabetes. The dimensions of the encapsulated tissue can impact the stresses placed on the tissue and ILK overexpression shows the ability to extend function of dissociated cells as well as intact islets. These results suggest that lost cell-extracellular matrix interactions in cell encapsulation systems can lead to decreased insulin secretion and ILK signaling is a target to overcome this phenomenon. (communication)

To understand how the balance between pro- and anti-apoptotic signals influences effector function in the immune system, we studied the X-linked inhibitor of apoptosis (XIAP), an endogenous regulator of cellular apoptosis. Real-time PCR showed increased XIAP expression in blood of mice...... and oligodendrocytes were not affected; neither did apoptosis increase in liver, where XIAP knockdown also occurred. ASO-XIAP increased susceptibility of T cells to activation-induced apoptosis in vitro. Our results identify XIAP as a critical controller of apoptotic susceptibility of effector T cell function...

Denitrification is mediated by microbial, and physicochemical, processes leading to nitrogen loss via N2O and N2 emissions. Soil pH regulates the reduction of N2O to N2, however, it can also affect microbial community composition and functional potential. Here we simultaneously test the link between pH, community composition, and the N2O emission ratio (N2O/(NO + N2O + N2)) in 13 temperate pasture soils. Physicochemical analysis, gas kinetics, 16S rRNA amplicon sequencing, metagenomic and quantitative PCR (of denitrifier genes: nirS, nirK, nosZI and nosZII) analysis were carried out to characterize each soil. We found strong evidence linking pH to both N2O emission ratio and community changes. Soil pH was negatively associated with N2O emission ratio, while being positively associated with both community diversity and total denitrification gene (nir & nos) abundance. Abundance of nosZII was positively linked to pH, and negatively linked to N2O emissions. Our results confirm that pH imposes a general selective pressure on the entire community and that this results in changes in emission potential. Our data also support the general model that with increased microbial diversity efficiency increases, demonstrated in this study with lowered N2O emission ratio through more efficient conversion of N2O to N2.

We use the form factors of the quantum transfer matrix in the zero-temperature limit in order to study the two-point ground-state correlation functions of the XXZ chain in the antiferromagnetic massive regime. We obtain novel form factor series representations of the correlation functions which differ from those derived either from the q-vertex-operator approach or from the algebraic Bethe Ansatz approach to the usual transfer matrix. We advocate that our novel representations are numerically more efficient and allow for a straightforward calculation of the large-distance asymptotic behaviour of the two-point functions. Keeping control over the temperature corrections to the two-point functions we see that these are of order $T^\\infty$ in the whole antiferromagnetic massive regime. The isotropic limit of our result yields a novel form factor series representation for the two-point correlation functions of the XXX chain at zero magnetic field.

This paper addresses one major cause for large uncertainties in human reliability analysis (HRA) results, that is, an absence of detailed function, task, timeline, link and human vulnerability analyses. All too often this crucial step in the HRA process is done in a cursory fashion using word of mouth or written procedures which themselves may incompletely or inaccurately represent the human action sequences and human error vulnerabilities being analyzed. The paper examines the potential contributions these detailed analyses can make in achieving quantitative and qualitative HRA results which are: (1) creditable, that is, minimize uncertainty, (2) auditable, that is, systematically linking quantitative results and qualitative information from which the results are derived, (3) capable of supporting root cause analyses on human reliability factors determined to be major contributors to risk, and (4) capable of repeated measures and being combined with similar results from other analyses to examine HRA issues transcending individual systems and facilities. Based on experience analyzing test and commercial nuclear reactors, and medical applications of nuclear technology, an iterative process is suggested for doing detailed function, task, timeline, link and human vulnerability analyses using documentation reviews, open-ended and structured interviews, direct observations, and group techniques. Finally, the paper concludes that detailed analyses done in this manner by knowledgeable human factors practitioners, can contribute significantly to the credibility, auditability, causal factor analysis, and combining goals of the HRA.

Microorganisms drive biogeochemical processes, but linking these processes to real changes in microbial communities under field conditions is not trivial. Here, we present a model-based approach to estimate independent contributions of microbial community shifts to ecosystem properties. The approach was tested empirically, using denitrification potential as our model process, in a spatial survey of arable land encompassing a range of edaphic conditions and two agricultural production systems. Soil nitrate was the most important single predictor of denitrification potential (the change in Akaike's information criterion, corrected for sample size, ΔAIC(c) = 20.29); however, the inclusion of biotic variables (particularly the evenness and size of denitrifier communities [ΔAIC(c) = 12.02], and the abundance of one denitrifier genotype [ΔAIC(c) = 18.04]) had a substantial effect on model precision, comparable to the inclusion of abiotic variables (biotic R2 = 0.28, abiotic R2 = 0.50, biotic + abiotic R2 = 0.76). This approach provides a valuable tool for explicitly linking microbial communities to ecosystem functioning. By making this link, we have demonstrated that including aspects of microbial community structure and diversity in biogeochemical models can improve predictions of nutrient cycling in ecosystems and enhance our understanding of ecosystem functionality.

Full Text Available Continental particulate organic matter (POM plays a major role in the functioning of coastal marine ecosystems as a disturbance as well as an input of nutrients. Relationships linking continental inputs from the Rhone River to biodiversity of the coastal benthic ecosystem and fishery production were investigated in the Golfe du Lion (NW Mediterranean Sea. Macrobenthic community diversity decreased when continen¬tal inputs of organic matter increased, whereas ecosystem production, measured by common sole (Solea solea fishery yields in the area, increased. Decreases in macrobenthic diversity were mainly related to an increasing abundance of species with specific functional traits, particularly deposit-feeding polychaetes. The decrease in macrobenthic diversity did not result in a decrease, but an increase in ecosystem production, as it enhanced the transfer of continental POM into marine food webs. The present study showed that it is necessary to consider functional traits of species, direct and indirect links between species, and feedback loops to understand the effects of biodiversity on ecosystem functioning and productivity.

Complexes of specific assembly factors and generic endoplasmic reticulum (ER) chaperones, collectively called the MHC class I peptide-loading complex (PLC), function in the folding and assembly of MHC class I molecules. The glycan-binding chaperone calreticulin (CRT) and partner oxidoreductase ERp57 are important in MHC class I assembly, but the sequence of assembly events and specific interactions involved remain incompletely understood. We show that the recruitments of CRT and ERp57 to the PLC are codependent and also dependent upon the ERp57 binding site and the glycan of the assembly factor tapasin. Furthermore, the ERp57 binding site and the glycan of tapasin enhance β(2)m and MHC class I heavy (H) chain recruitment to the PLC, with the ERp57 binding site having the dominant effect. In contrast, the conserved MHC class I H chain glycan played a minor role in CRT recruitment into the PLC, but impacted the recruitment of H chains into the PLC, and glycan-deficient H chains were impaired for tapasin-independent and tapasin-assisted assembly. The conserved MHC class I glycan and tapasin facilitated an early step in the assembly of H chain-β(2)m heterodimers, for which tapasin-ERp57 or tapasin-CRT complexes were not required. Together, these studies provide insights into how PLCs are constructed, demonstrate two distinct mechanisms by which PLCs can be stabilized, and suggest the presence of intermediate H chain-deficient PLCs.

Full Text Available Odor detection thresholds (ODTs are used for assessing outdoor and indoor air quality. They are obtained experimentally by olfactometry and psychophysical methods, and large compilations are available in the literature. A non-linear regression equation was fitted to describe the ODT variability of 114 aliphatic compounds based on the alkyl chain length for different homologous series (carboxylic acids, aldehydes, 2-ketones, esters, 1-alcohols, amines, thiols, thioethers and hydrocarbons. The resulting equation reveals an effect of the functional group, molecular size and also an interaction between both factors. Although the mechanistic interpretation of results is uncertain, the relatively high goodness-of-fit (R2 = 0.90 suggests that ODT values of aliphatic compounds can be predicted rather accurately, which is not the case for rigid molecules. This equation may serve as a basis for the development of more complex ODT models taking into account diverse structural features of odorants. The variability of power-law exponents was also investigated for the homologous series.

The mammalian pineal gland is a prominent secretory organ with a high metabolic activity. Melatonin (N-acetyl-5-methoxytryptamine), the main secretory product of the pineal gland, efficiently scavenges both the hydroxyl and peroxyl radicals counteracting lipid peroxidation in biological membranes. Approximately 25% of the total fatty acids present in the rat pineal lipids are represented by arachidonic acid (20:4n-6) and docosahexaenoic acid (22:6n-3). These very long chain polyunsaturated fatty acids play important roles in the pineal gland. In addition to the production of melatonin, the mammalian pineal gland is able of convert these polyunsaturated fatty acids into bioactive lipid mediators. Lipoxygenation is the principal lipoxygenase (LOX) activity observed in the rat pineal gland. Lipoxygenation in the pineal gland is exceptional because no other brain regions express significant LOX activities under normal physiological conditions. The rat pineal gland expresses both 12- and 15-lipoxygenase (LOX) activities, producing 12- and 15-hydroperoxyeicosatetraenoic acid (12- and 15-HpETE) from arachidonic acid and 14- and 17-hydroxydocosahexaenoic acid (14- and 17-HdoHE) from docosahexaenoic acid, respectively. The rat pineal also produces hepoxilins via LOX pathways. The hepoxilins are bioactive epoxy-hydroxy products of the arachidonic acid metabolism via the 12S-lipoxygenase (12S-LOX) pathway. The two key pineal biochemical functions, lipoxygenation and melatonin synthesis, may be synergistically regulated by the status of n-3 essential fatty acids.

DNA-incorporating hydrophobic moieties can be synthesized by either solid-phase or solution-phase coupling. On a solid support the DNA is protected, and hydrophobic units are usually attached employing phosphoramidite chemistry involving a DNA synthesizer. On the other hand, solution coupling in aqueous medium results in low yields due to the solvent incompatibility of DNA and hydrophobic compounds. Hence, the development of a general coupling method for producing amphiphilic DNA conjugates with high yield in solution remains a major challenge. Here, we report an organic-phase coupling strategy for nucleic acid modification and polymerization by introducing a hydrophobic DNA-surfactant complex as a reactive scaffold. A remarkable range of amphiphile-DNA structures (DNA-pyrene, DNA-triphenylphosphine, DNA-hydrocarbon, and DNA block copolymers) and a series of new brush-type DNA side-chain homopolymers with high DNA grafting density are produced efficiently. We believe that this method is an important breakthrough in developing a generalized approach to synthesizing functional DNA molecules for self-assembly and related technological applications.

The invariant chain (Ii) is a multifunctional protein, which has an essential role in the assembly and transport of major histocompatibility complex class II (MHC II) molecules. From a single gene, Ii is synthesized as four different isoforms: Iip33, Iip35, Iip41 and Iip43. Iip35 and Iip43 are specific to humans, and are formed due to an upstream alternative translation site, resulting in an N-terminal extension of 16 amino acids. This extension harbors a strong endoplasmic reticulum (ER) retention motif. Consequently, Iip35 or Iip43 expressed alone are retained in the ER, whereas Iip33 and Iip41 rapidly traffic to the endosomal pathway. Endogenously expressed, the four isoforms form mixed heterotrimers in the ER; however, mainly due to the absence of the Iip35/p43 isoforms in mice, little is known about how they influence general Ii function. In this study, we have co-expressed Iip33 and Iip35 in human cells with and without MHC II to gain a better understanding of how Iip35 isoform influences the cellular properties of Iip33. We find that Iip35 significantly affects the properties of Iip33. In the presence of Iip35, the transport of Iip33 out of the ER is delayed, its half-life is dramatically prolonged and its ability to induce enlarged endosomes and delayed endosomal maturation is abrogated.

Full Text Available Subject of Research. We analyze the problems of finite Markov chains apparatus application for simulating a human operator activity in the quasi-static functional environment. It is shown that the functional environment stochastic nature is generated by a factor of interval character of human operator properties. Method. The problem is solved in the class of regular (recurrent finite Markov chains with three states of the human operator: with a favorable, median and unfavorable combination of the values of mathematical model parameters of the human operator in a quasi-static functional environment. The finite Markov chain is designed taking into account the factors of human operator tiredness and interval character of parameters of the model representation of his properties. The device is based on the usage of mathematical approximation of the standard curve of the human operator activity performance during work shift. The standard curve of the human operator activity performance is based on the extensive research experience of functional activity of the human operator with the help of photos of the day, his action timing and ergonomic generalizations. Main Results. The apparatus of regular finite Markov chains gave the possibility to evaluate correctly the human operator activity performance in a quasi-static functional environment with the use of the main information component of these chains as a vector of final probabilities. In addition, we managed to build an algorithmic basis for estimating the stationary time (time study for transit of human operator from arbitrary initial functional state into a state corresponding to a vector of final probabilities for a used chain after it reaches the final state based on the analysis of the eigenvalues spectrum of the matrix of transition probabilities for a regular (recurrent finite Markov chain. Practical Relevance. Obtained theoretical results are confirmed by illustrative examples, which

An ingenious system evolved to facilitate insulin binding to the insulin receptor as a monomer and at the same time ensure sufficient stability of insulin during storage. Insulin dimer is the cornerstone of this system. Insulin dimer is relatively weak, which ensures dissociation into monomers...... in the circulation, and it is stabilized by hexamer formation in the presence of zinc ions during storage in the pancreatic ß-cell. Due to the transient nature of insulin dimer, direct investigation of this important form is inherently difficult. To address the relationship between insulin oligomerization...... and insulin stability and function, we engineered a covalently linked insulin dimer in which two monomers were linked by a disulfide bond. The structure of this covalent dimer was identical to the self-association dimer of human insulin. Importantly, this covalent dimer was capable of further oligomerization...

The myosin essential light chain (ELC) is a structural component of the actomyosin cross-bridge, but its function is poorly understood, especially the role of the cardiac specific N-terminal extension in modulating actomyosin interaction. Here, we generated transgenic (Tg) mice expressing the A57G (alanine to glycine) mutation in the cardiac ELC known to cause familial hypertrophic cardiomyopathy (FHC). The function of the ELC N-terminal extension was investigated with the Tg-{Delta}43 mouse model, whose myocardium expresses a truncated ELC. Low-angle X-ray diffraction studies on papillary muscle fibers in rigor revealed a decreased interfilament spacing ({approx} 1.5 nm) and no alterations in cross-bridge mass distribution in Tg-A57G mice compared to Tg-WT, expressing the full-length nonmutated ELC. The truncation mutation showed a 1.3-fold increase in I{sub 1,1}/I{sub 1,0}, indicating a shift of cross-bridge mass from the thick filament backbone toward the thin filaments. Mechanical studies demonstrated increased stiffness in Tg-A57G muscle fibers compared to Tg-WT or Tg-{Delta}43. The equilibrium constant for the cross-bridge force generation step was smallest in Tg-{Delta}43. These results support an important role for the N-terminal ELC extension in prepositioning the cross-bridge for optimal force production. Subtle changes in the ELC sequence were sufficient to alter cross-bridge properties and lead to pathological phenotypes.

Full Text Available Abstract Background Conventional fluorescent proteins, such as GFP, its derivatives and flavin mononucleotide based fluorescent proteins (FbFPs are often used as fusion tags for detecting recombinant proteins during cultivation. These reporter tags are state-of-the-art; however, they have some drawbacks, which can make on-line monitoring challenging. It is discussed in the literature that the large molecular size of proteins of the GFP family may stress the host cell metabolism during production. In addition, fluorophore formation of GFP derivatives is oxygen-dependent resulting in a lag-time between expression and fluorescence detection and the maturation of the protein is suppressed under oxygen-limited conditions. On the contrary, FbFPs are also applicable in an oxygen-limited or even anaerobic environment but are still quite large (58% of the size of GFP. Results As an alternative to common fluorescent tags we developed five novel tags based on clustered tryptophan residues, called W-tags. They are only 5-11% of the size of GFP. Based on the property of tryptophan to fluoresce in absence of oxygen it is reasonable to assume that the functionality of our W-tags is also given under anaerobic conditions. We fused these W-tags to a recombinant protein model, the anti-CD30 receptor single-chain fragment variable antibody (scFv Ki-4(scFv and the anti-MucI single-chain fragment variable M12(scFv. During cultivation in Microtiter plates, the overall tryptophan fluorescence intensity of all cultures was measured on-line for monitoring product formation via the different W-tags. After correlation of the scattered light signal representing biomass concentration and tryptophan fluorescence for the uninduced cultures, the fluorescence originating from the biomass was subtracted from the overall tryptophan signal. The resulting signal, thus, represents the product fluorescence of the tagged and untagged antibody fragments. The product fluorescence signal

In this paper, a predator-prey chain system with impulsive effects and Beddington-DeAngelis functional response is studied. We investigate the existence of periodic solu-tion by coincidence degree theory. Sufficient conditions are obtained for the existence of periodic solution.

Full Text Available A new homologous series of thermally stable thermotropic liquid crystalline poly(azomethine-ethers based on thiazole moiety were synthesized by solution polycondensation of 4,4`-diformyl-α,ω-diphenoxyalkanes, I–IV or 4,4`-diformyl-2,2`-dimethoxy-α,ω-diphenoxyalkanes V–VIII with the new bis(2-aminothiazole monomer X. A model compound XI was synthesized from X with benzaldehyde and characterized by elemental and spectral analyses. The inherent viscosities of the resulting polymers were in the range 0.43–1.34 dI/g. All the poly(azomethine-ethers were insoluble in common organic solvents but dissolved completely in concentrated H2SO4 and formic acid. The mesomorphic properties of these polymers were studied as a function of the diphenoxyalkane space length. Their thermotropic liquid crystalline properties were examined by DSC and optical polarizing microscopy and demonstrated that the resulting polymers form nematic mesophases over wide temperature ranges. The thermogravimetric analyses of those polymers were evaluated by TGA and DSC measurements and correlated to their structural units. X-ray analysis showed that polymers having some degree of crystallinity in the region 2θ = 5–60°. In addition, the morphological properties of selected examples were tested by scanning electron microscopy.

It is increasingly understood that in the aging brain, especially in the case of patients suffering from neurodegenerative diseases, some fatty acids at pathologically high concentrations exert detrimental activities. To study such activities, we here analyze genetic diseases, which are due to compromised metabolism of specific fatty acids, either the branched-chain phytanic acid or very long-chain fatty acids (VLCFAs). Micromolar concentrations of phytanic acid or of VLCFAs disturb the integrity of neural cells by impairing Ca(2+) homeostasis, enhancing oxidative stress or de-energizing mitochondria. Finally, these combined harmful activities accelerate cell death. Mitochondria are more severely targeted by phytanic acid than by VLCFAs. The insertion of VLCFAs into the inner membrane distorts the arrangement of membrane constituents and their functional interactions. Phytanic acid exerts specific protonophoric activity, induces reactive oxygen species (ROS) generation, and reduces ATP generation. A clear inhibition of the Na(+), K(+)-ATPase activity by phytanic acid has also been reported. In addition to the instantaneous effects, a chronic exposure of brain cells to low micromolar concentrations of phytanic acid may produce neuronal damage in Refsum disease by altering epigenetic transcriptional regulation. Myelin-producing oligodendrocytes respond with particular sensitivity to VLCFAs. Deleterious activity of VLCFAs on energy-dependent mitochondrial functions declines with increasing the hydrocarbon chain length (C22:0 > C24:0 > C26:0). In contrast, the reverse sequence holds true for cell death induction by VLCFAs (C22:0 fatty acid-mediated neurodegeneration and should help to provide possible therapeutic interventions.

Extensive research has investigated links between individual differences in youths' autonomic nervous system (ANS) functioning and psychological outcomes related to emotion regulation, yet little of this research has examined developmental change. The study tested whether individual differences in youths' tonic and stress-induced ANS functioning, assessed at age 14, and changes in ANS functioning from age 14 to 16 predicted corresponding changes in youths' behavioral warmth, as displayed during videotaped mother-child conflict interactions conducted at age 14 and 16. Increased behavioral warmth was predicted by increased baseline respiratory sinus arrhythmia (RSA), increased SCL stress reactivity, decreased RSA stress reactivity (i.e., greater vagal suppression), and decreased baseline SCL. There was also an interaction between RSA stress reactivity at age 14 and changes in maternal warmth from age 14 to 16, such that increased maternal warmth was only associated with increased adolescent warmth for adolescents with lower RSA stress reactivity at age 14.

A BRIEF HISTORY OF THE DEVELOPMENT OF CHAINEarly DevelopmentsCog ChainCast Detachable ChainCast Pintle ChainPrecision Roller ChainEngineering Steel ChainSilent ChainFlat-Top ChainTerminologyA CHAIN OVERVIEW: USES AND ADVANTAGESGeneralTypes of ChainScope of Chains CoveredStyles and Forms of ChainsStraight and Offset LinkChainsChains With and Without RollersUses of ChainStandard Chains and Their UsesThe Advantages of Chains in ApplicationsAdvantages of Roller Chains in DrivesAdvantages of Silent Chain Drives

To understand how the balance between pro- and anti-apoptotic signals influences effector function in the immune system, we studied the X-linked inhibitor of apoptosis (XIAP), an endogenous regulator of cellular apoptosis. Real-time PCR showed increased XIAP expression in blood of mice with exper......To understand how the balance between pro- and anti-apoptotic signals influences effector function in the immune system, we studied the X-linked inhibitor of apoptosis (XIAP), an endogenous regulator of cellular apoptosis. Real-time PCR showed increased XIAP expression in blood of mice...... with experimental autoimmune encephalomyelitis, correlating with disease severity. Daily administration (10 mg/kg/day i.p.) of a 19-mer antisense oligonucleotide specific for XIAP (ASO-XIAP) abolished disease-associated XIAP mRNA and protein expression, and given from day of onset, alleviated experimental...... and oligodendrocytes were not affected; neither did apoptosis increase in liver, where XIAP knockdown also occurred. ASO-XIAP increased susceptibility of T cells to activation-induced apoptosis in vitro. Our results identify XIAP as a critical controller of apoptotic susceptibility of effector T cell function...

Highlights: • Equilibrium, kinetic and thermodynamic of adsorption of dyes onto PDVB-IL was investigated. • PDVB-IL has a high adsorption capacity to treat dyes solution. • Higher adsorption capacity is due to the functional groups of PDVB-IL. • Molecular structure of dyes influences the adsorption capacity. -- Abstract: A novel functional ionic liquid based cross-linked polymer (PDVB-IL) was synthesized from 1-aminoethyl-3-vinylimidazolium chloride and divinylbenzene for use as an adsorbent. The physicochemical properties of PDVB-IL were investigated by Fourier transform infrared spectroscopy, scanning electron microscopy and thermogravimetric analysis. The adsorptive capacity was investigated using anionic azo dyes of orange II, sunset yellow FCF, and amaranth as adsorbates. The maximum adsorption capacity could reach 925.09, 734.62, and 547.17 mg/g for orange II, sunset yellow FCF and amaranth at 25 °C, respectively, which are much better than most of the other adsorbents reported earlier. The effect of pH value was investigated in the range of 1–8. The result shows that a low pH value is found to favor the adsorption of those anionic azo dyes. The adsorption kinetics and isotherms are well fitted by a pseudo second-order model and Langmuir model, respectively. The adsorption process is found to be dominated by physisorption. The introduction of functional ionic liquid moieties into cross-linked poly(divinylbenzene) polymer constitutes a new and efficient kind of adsorbent.

Full Text Available Staphylococcus aureus enterotoxins have immunomodulatory properties. In this study, we show that Staphylococcal enterotoxin A (SEA induces a strong proliferative response in a murine T cell clone independent of MHC class II bearing cells. SEA stimulation also induces a state of hypo-responsiveness (anergy. We characterized the components of the T cell receptor (TCR during induction of anergy by SEA. Most interestingly, TCR zeta chain phosphorylation was absent under SEA anergizing conditions, which suggests an uncoupling of zeta chainfunction. We characterize here a model system for studying anergy in the absence of confounding costimulatory signals.

Full Text Available Abstract Background Successful protein structure prediction requires accurate low-resolution scoring functions so that protein main chain conformations that are close to the native can be identified. Once that is accomplished, a more detailed and time-consuming treatment to produce all-atom models can be undertaken. The earliest low-resolution scoring used simple distance-based "contact potentials," but more recently, the relative orientations of interacting amino acids have been taken into account to improve performance. Results We developed a new knowledge-based scoring function, LoCo, that locates the interaction partners of each individual residue within a local coordinate system based only on the position of its main chain N, Cα and C atoms. LoCo was trained on a large set of experimentally determined structures and optimized using standard sets of modeled structures, or "decoys." No structure used to train or optimize the function was included among those used to test it. When tested against 29 other published main chainfunctions on a group of 77 commonly used decoy sets, our function outperformed all others in Cα RMSD rank of the best-scoring decoy, with statistically significant p-values Conclusions Our function demonstrates an unmatched combination of accuracy, speed, and simplicity and shows excellent promise for protein structure prediction. Broader applications may include protein-protein interactions and protein design.

Full Text Available Emerging technologies such as Software-Defined Networks (SDN and Network Function Virtualization (NFV promise to address cost reduction and flexibility in network operation while enabling innovative network service delivery models. However, operational network service delivery solutions still need to be developed that actually exploit these technologies, especially at the multi-provider level. Indeed, the implementation of network functions as software running over a virtualized infrastructure and provisioned on a service basis let one envisage an ecosystem of network services that are dynamically and flexibly assembled by orchestrating Virtual Network Functions even across different provider domains, thereby coping with changeable user and service requirements and context conditions. In this paper we propose an approach that adopts Service-Oriented Architecture (SOA technology-agnostic architectural guidelines in the design of a solution for orchestrating and dynamically chaining Virtual Network Functions. We discuss how SOA, NFV, and SDN may complement each other in realizing dynamic network functionchaining through service composition specification, service selection, service delivery, and placement tasks. Then, we describe the architecture of a SOA-inspired NFV orchestrator, which leverages SDN-based network control capabilities to address an effective delivery of elastic chains of Virtual Network Functions. Preliminary results of prototype implementation and testing activities are also presented. The benefits for Network Service Providers are also described that derive from the adaptive network service provisioning in a multi-provider environment through the orchestration of computing and networking services to provide end users with an enhanced service experience.

Full Text Available An ingenious system evolved to facilitate insulin binding to the insulin receptor as a monomer and at the same time ensure sufficient stability of insulin during storage. Insulin dimer is the cornerstone of this system. Insulin dimer is relatively weak, which ensures dissociation into monomers in the circulation, and it is stabilized by hexamer formation in the presence of zinc ions during storage in the pancreatic β-cell. Due to the transient nature of insulin dimer, direct investigation of this important form is inherently difficult. To address the relationship between insulin oligomerization and insulin stability and function, we engineered a covalently linked insulin dimer in which two monomers were linked by a disulfide bond. The structure of this covalent dimer was identical to the self-association dimer of human insulin. Importantly, this covalent dimer was capable of further oligomerization to form the structural equivalent of the classical hexamer. The covalently linked dimer neither bound to the insulin receptor, nor induced a metabolic response in vitro. However, it was extremely thermodynamically stable and did not form amyloid fibrils when subjected to mechanical stress, underlining the importance of oligomerization for insulin stability.

Porous inorganic capillary membranes are prepared to serve as model structures for the experimental investigation of the gas transport in functionalized mesopores. The porous structures possess a mean pore diameter of 23 nm which is slightly reduced to 20 nm after immobilizing C16-alkyl chains on the surface. Gas permeation measurements are performed at temperatures ranging from 0 to 80 °C using Ar, N2, and CO2. Nonfunctionalized structures feature a gas transport according to Knudsen diffusion with regard to gas flow and selectivity. After C16-functionalization, the gas flow is reduced by a factor of 10, and the ideal selectivities deviate from the Knudsen theory. CO2 adsorption measurements show a decrease in total amount of adsorbed gas and isosteric heat of adsorption. It is hypothesized that the immobilized C16-chains sterically influence the gas transport behavior without a contribution from adsorption effects. The reduced gas flow derives from an additional surface resistance caused by the C16-chains spacially limiting the adsorption and desorption directions for gas molecules propagating through the structure, resulting in longer diffusion paths. In agreement, the gas flow is found to correlate with the molecular diameter of the gas species (CO2 ideal selectivities with the relation [Formula: see text]. The influence on selectivity increases with increasing temperature which leads to the conclusion that the temperature induced movement of the C16-chains is responsible for the stronger interaction between gas molecules and surface functional groups.

The extension of very-long-chain fatty acids (VLCFAs) for the synthesis of specialized apoplastic lipids requires unique biochemical machinery. Condensing enzymes catalyze the first reaction in fatty acid elongation and determine the chain length of fatty acids accepted and produced by the fatty acid elongation complex. Although necessary for the elongation of all VLCFAs, known condensing enzymes cannot efficiently synthesize VLCFAs longer than 28 carbons, despite the prevalence of C28 to C34 acyl lipids in cuticular wax and the pollen coat. The eceriferum2 (cer2) mutant of Arabidopsis (Arabidopsis thaliana) was previously shown to have a specific deficiency in cuticular waxes longer than 28 carbons, and heterologous expression of CER2 in yeast (Saccharomyces cerevisiae) demonstrated that it can modify the acyl chain length produced by a condensing enzyme from 28 to 30 carbon atoms. Here, we report the physiological functions and biochemical specificities of the CER2 homologs CER2-LIKE1 and CER2-LIKE2 by mutant analysis and heterologous expression in yeast. We demonstrate that all three CER2-LIKEs function with the same small subset of condensing enzymes, and that they have different effects on the substrate specificity of the same condensing enzyme. Finally, we show that the changes in acyl chain length caused by each CER2-LIKE protein are of substantial importance for cuticle formation and pollen coat function.

Respirable quartz dust has been classified as a human carcinogen by the International Agency for Research on Cancer. The aim of our study was to investigate the mechanisms of DNA damage by DQ12 quartz in RLE-6TN rat lung epithelial type II cells (RLE). Transmission electron microscopy and flow-cytometry analysis showed a rapid particle uptake (30 min to 4 h) of quartz by the RLE cells, but particles were not found within the cell nuclei. This suggests that DNA strand breakage and induction of 8-hydroxydeoxyguanosine - as also observed in these cells during these treatment intervals - did not result from direct physical interactions between particles and DNA, or from short-lived particle surface-derived reactive oxygen species. DNA damage by quartz was significantly reduced in the presence of the mitochondrial inhibitors rotenone and antimycin-A. In the absence of quartz, these inhibitors did not affect DNA damage, but they reduced cellular oxygen consumption. No signs of apoptosis were observed by quartz. Flow-cytometry analysis indicated that the reduced DNA damage by rotenone was not due to a possible mitochondria-mediated reduction of particle uptake by the RLE cells. Further proof of concept for the role of mitochondria was shown by the failure of quartz to elicit DNA damage in mitochondria-depleted 143B (rho-0) osteosarcoma cells, at concentrations where it elicited DNA damage in the parental 143B cell line. In conclusion, our data show that respirable quartz particles can elicit oxidative DNA damage in vitro without entering the nuclei of type II cells, which are considered to be important target cells in quartz carcinogenesis. Furthermore, our observations indicate that such indirect DNA damage involves the mitochondrial electron transport chainfunction, by an as-yet-to-be elucidated mechanism.

Full Text Available Sapovirus, a member of the Caliciviridae family, is an important cause of acute gastroenteritis in humans and pigs. Currently, the porcine sapovirus (PSaV Cowden strain remains the only cultivable member of the Sapovirus genus. While some caliciviruses are known to utilize carbohydrate receptors for entry and infection, a functional receptor for sapovirus is unknown. To characterize the functional receptor of the Cowden strain of PSaV, we undertook a comprehensive series of protein-ligand biochemical assays in mock and PSaV-infected cell culture and/or piglet intestinal tissue sections. PSaV revealed neither hemagglutination activity with red blood cells from any species nor binding activity to synthetic histo-blood group antigens, indicating that PSaV does not use histo-blood group antigens as receptors. Attachment and infection of PSaV were markedly blocked by sialic acid and Vibrio cholerae neuraminidase (NA, suggesting a role for α2,3-linked, α2,6-linked or α2,8-linked sialic acid in virus attachment. However, viral attachment and infection were only partially inhibited by treatment of cells with sialidase S (SS or Maackia amurensis lectin (MAL, both specific for α2,3-linked sialic acid, or Sambucus nigra lectin (SNL, specific for α2,6-linked sialic acid. These results indicated that PSaV recognizes both α2,3- and α2,6-linked sialic acids for viral attachment and infection. Treatment of cells with proteases or with benzyl 4-O-β-D-galactopyranosyl-β-D-glucopyranoside (benzylGalNAc, which inhibits O-linked glycosylation, also reduced virus binding and infection, whereas inhibition of glycolipd synthesis or N-linked glycosylation had no such effect on virus binding or infection. These data suggest PSaV binds to cellular receptors that consist of α2,3- and α2,6-linked sialic acids on glycoproteins attached via O-linked glycosylation.

Sapovirus, a member of the Caliciviridae family, is an important cause of acute gastroenteritis in humans and pigs. Currently, the porcine sapovirus (PSaV) Cowden strain remains the only cultivable member of the Sapovirus genus. While some caliciviruses are known to utilize carbohydrate receptors for entry and infection, a functional receptor for sapovirus is unknown. To characterize the functional receptor of the Cowden strain of PSaV, we undertook a comprehensive series of protein-ligand biochemical assays in mock and PSaV-infected cell culture and/or piglet intestinal tissue sections. PSaV revealed neither hemagglutination activity with red blood cells from any species nor binding activity to synthetic histo-blood group antigens, indicating that PSaV does not use histo-blood group antigens as receptors. Attachment and infection of PSaV were markedly blocked by sialic acid and Vibrio cholerae neuraminidase (NA), suggesting a role for α2,3-linked, α2,6-linked or α2,8-linked sialic acid in virus attachment. However, viral attachment and infection were only partially inhibited by treatment of cells with sialidase S (SS) or Maackia amurensis lectin (MAL), both specific for α2,3-linked sialic acid, or Sambucus nigra lectin (SNL), specific for α2,6-linked sialic acid. These results indicated that PSaV recognizes both α2,3- and α2,6-linked sialic acids for viral attachment and infection. Treatment of cells with proteases or with benzyl 4-O-β-D-galactopyranosyl-β-D-glucopyranoside (benzylGalNAc), which inhibits O-linked glycosylation, also reduced virus binding and infection, whereas inhibition of glycolipd synthesis or N-linked glycosylation had no such effect on virus binding or infection. These data suggest PSaV binds to cellular receptors that consist of α2,3- and α2,6-linked sialic acids on glycoproteins attached via O-linked glycosylation.

In this report, the peptide linker connecting scFv VH and VL domains were genetically modified to contain different amino acids (i.e. cysteine (scFv-cys) or histidines ( scFv-his)) to enable the scFv to adsorb or self-assemble onto the gold nanoparticles (NPs). The scFv-cys stabilized gold NPs were used to develop a highly sensitive colorimetric immunosensor. The scFv-cys stabilized gold NPs were characterized by UV-vis spectra, transmission electron microscope (TEM) and FT-IR. After adding the antigen rabbit IgG, the solution of scFv-cys stabilized gold NPs shows obvious visible color change from deep red to light purple due to the aggregation of the gold nanoparticles. Based on the colorimetric aggregation of scFv-cys stabilized gold NPs, the immunosensor exhibits high sensitivity with detection limit of 1.7 nM and good specificity. The good properties of the colorimetric aggregation immunosensor would be attributed to the small size of scFv and the covalent link between the scFv and gold NPs that improve the better orientation and enhance the probe density. With the advantages of speed, simplicity and specificity, the colorimetric immunoassay based on the functionalized scFv stabilized gold NPs represents a promising approach for protein analysis and clinical diagnostics. PMID:19327975

Major depression is associated with impairments of executive functions and affect perception deficits, both being linked to dysfunction of fronto-subcortical networks. So far, little is known about the relationship between cognitive and affective deficits in major depression. In the present investigation, affect perception and executive functions were assessed in 29 patients with a diagnosis of major depression (Dep) and 29 healthy controls (HC). Both groups were comparable on IQ, age, and gender distribution. Depressed patients showed deficits of perception of affective prosody, which were significantly related to inhibition, set shifting, and working memory. Our findings suggest a significant association between cognitive deficits and affect perception impairments in major depression, which may be of considerable clinical relevance and might be addressed in treatment approaches. Future studies are desirable to investigate the nature of the association in more detail.

Full Text Available This paper presents a specific structure of neural network as the functionallink artificial neural network (FLANN. This technique has been employed for classification tasks of data mining. In fact, there are a few studies that used this tool for solving classification problems. In this present research, we propose a hybrid FLANN (HFLANN model, where the optimization process is performed using 3 known population based techniques such as genetic algorithms, particle swarm and differential evolution. This model will be empirically compared to FLANN based back-propagation algorithm and to others classifiers as decision tree, multilayer perceptron based back-propagation algorithm, radical basic function, support vector machine, and K-nearest Neighbor. Our results proved that the proposed model outperforms the other single model. (Abstract

Slowed information processing speed (IPS) is frequently reported in those with multiple sclerosis (MS), and at least 20% are compromised on some aspect of executive functioning also. However, any relationship between these two processes has not been examined. The Sternberg Memory Scanning Test, Processing Speed Index (WAIS-III), Delis Kaplan Executive Function System (D.KEFS), and Working Memory Index (WMS-III) were administered to 90 participants with MS. Their performance on the PSI was significantly below the normative scores but no deficits in memory scanning speed were evident. The initial response speed of the Sternberg and the PSI were more closely related to D.KEFS performance, particularly in timed tasks with a high cognitive demand (switching tasks). In contrast, memory scanning speed was related to working memory. This study reinforces the link between IPS and working memory in MS, and supports the suggestion that IPS is not a unitary construct.

Protein glycosylation pathways are conserved metabolic processes in eukaryotic organisms and are required for cell fitness. In fungal pathogens, the N-linked glycosylation pathway is indispensable for proper cell wall composition and virulence. In Sporothrix schenckii sensu stricto, the causative agent of sporotrichosis, little is known about this glycosylation pathway. Here, using a genome-wide screening for putative members of the glycosyl hydrolase (CAZy - GH) families 47 and 63, which group enzymes involved in the processing step during N-linked glycan maturation, we found seven homologue genes belonging to family 47 and one to family 63. The eight genes were individually expressed in C. albicans null mutants lacking either MNS1 (for members of family 47) or CWH41 (for the member of family 63). Our results indicate that SsCWH41 is the functional ortholog of CaCWH41, whereas SsMNS1 is the functional ortholog of CaMNS1. The remaining genes of family 47 encode Golgi mannosidases and endoplasmic reticulum degradation-enhancing alpha-mannosidase-like proteins (EDEMs). Since these GH families gather proteins used as target for drugs to control cell growth, identification of these genes could help in the design of antifungals that could be used to treat sporotrichosis and other fungal diseases. In addition, to our knowledge, we are the first to report that Golgi mannosidases and EDEMs are expressed and characterized in yeast cells.

Full Text Available Abstract Background The completion of maize genome sequencing has resulted in the identification of a large number of uncharacterized genes. Gene annotation and functional characterization of gene products are important to uncover novel protein functionality. Results In this paper, we identify, and annotate members of all the maize aldehyde dehydrogenase (ALDH gene superfamily according to the revised nomenclature criteria developed by ALDH Gene Nomenclature Committee (AGNC. The maize genome contains 24 unique ALDH sequences encoding members of ten ALDH protein families including the previously identified male fertility restoration RF2A gene, which encodes a member of mitochondrial class 2 ALDHs. Using computational modeling analysis we report here the identification, the physico-chemical properties, and the amino acid residue analysis of a novel tunnel like cavity exclusively found in the maize sterility restorer protein, RF2A/ALDH2B2 by which this protein is suggested to bind variably long chain molecular ligands and/or potentially harmful molecules. Conclusions Our finding indicates that maize ALDH superfamily is the most expanded of plant ALDHs ever characterized, and the mitochondrial maize RF2A/ALDH2B2 is the only plant ALDH that harbors a newly defined pocket/cavity with suggested functional specificity.

This document provides a study of the technical literature related to Command and Control (C2) link security for Unmanned Aircraft Systems (UAS) for operation in the National Airspace System (NAS). Included is a preliminary set of functional requirements for C2 link security.

From the human body structure composed of kinematic chain and its relationship with body functional training,this paper uses the method of documents and materials,logic analysis and other research methods,combined with the theoretical knowledge of functional anatomy, fascia, sports biomechanics, logic and other disciplines,to analyze the weak link and motion compensation in the functional training from kinematic chain perspective,and the core strength and stability in the role of functional training from the perspective of fascia chain.Also,the reasons for the weak link or even damage in the open chain and closed chain were analyzed and discussed, which has a positive practical significance in preventing and reducing sports inj uries, improving training efficiency and effectiveness.%从人体运动链构成的结构及其与身体功能性训练的关系入手，运用文献资料、逻辑分析等研究方法，综合借鉴功能解剖学、筋膜学、运动生物力学、逻辑学等学科的理论知识，以运动链的视角审视和分析功能性训练中的弱链、动作代偿等问题，运用筋膜链的视角对核心力量与稳定性在功能性训练中的作用，以及在开链－闭链在转链环节时出现弱链及损伤的原因进行分析与讨论，对于预防和减少运动损伤，提高训练效率和效益有着积极的现实意义。

Motivated by applications to higher-rank Brill-Noether theory and the Bertram-Feinberg-Mukai conjecture, we introduce the concepts of linked alternating and linked symplectic forms on a chain of vector bundles, and show that the linked symplectic Grassmannians parametrizing chains of subbundles isotropic for a given linked symplectic form has good dimensional behavior analogous to that of the classical symplectic Grassmannian.

Full Text Available Background: In most African and Arabic countries tuberculosis (TB causes great economic losses in bovine species and constitutes serious zoonotic problem. As the traditional diagnostic method delay the research because of low sensitivity and specificity, a rapid method of diagnosis is of outmost importance. Aim: The study was designed to evaluate the two rapid diagnostic methods of TB in cattle, further to differentiate between infected and bacillus Calmette-Guerin (BCG vaccinated animals. Materials and Methods: Intradermal tuberculin test was applied to 300 cattle. Of these cattle, 15 cattle were vaccinated from cattle negative to tuberculin test with BCG. Blood samples were taken for lymphocyte separation to apply polymerase chain reaction (PCR upon and for serum preparation for the enzyme-linked immunosorbent assay (ELISA application, this blood collected from 65 cattle classified into three groups, viz. positive tuberculin test (35 animals, negative tuberculin test (15 animals, and vaccinated cow with BCG (15 animals. From blood samples lymphocytes were separated and the isolated lymphocytes were subjected to PCR and serum for ELISA application. Blood samples, specimens from lymph nodes and specific tissues were taken for PCR and for cultivation and isolation of Mycobacterium bovis. Results and Conclusions: The results of this study revealed that PCR can be used as rapid efficient and accurate diagnostic test in detection of ruminant TB. Moreover, cattle′s ELISA reading showed higher sensitivity in positive tuberculin animals. However, the differentiations between vaccinated and infected animals not clear by using a single antigen only.

Chronic Chagas disease diagnosis relies on laboratory tests due to its clinical characteristics. The aim of this research was to review commercial enzyme-linked immunosorbent assay (ELISA) and polymerase chain reaction (PCR) diagnostic test performance. Performance of commercial ELISA or PCR for the diagnosis of chronic Chagas disease were systematically searched in PubMed, Scopus, Embase, ISI Web, and LILACS through the bibliography from 1980-2014 and by contact with the manufacturers. The risk of bias was assessed with QUADAS-2. Heterogeneity was estimated with the I2 statistic. Accuracies provided by the manufacturers usually overestimate the accuracy provided by academia. The risk of bias is high in most tests and in most QUADAS dimensions. Heterogeneity is high in either sensitivity, specificity, or both. The evidence regarding commercial ELISA and ELISA-rec sensitivity and specificity indicates that there is overestimation. The current recommendation to use two simultaneous serological tests can be supported by the risk of bias analysis and the amount of heterogeneity but not by the observed accuracies. The usefulness of PCR tests are debatable and health care providers should not order them on a routine basis. PCR may be used in selected cases due to its potential to detect seronegative subjects.

Enzyme-linked immunosorbent assay (ELISA) tests and polymerase chain reaction (PCR) may play a key role for early detection and treatment of human leptospirosis in developing countries. The aims of this study were to develop and validate an IgM ELISA under field conditions and to compare the diagnostic accuracy among IgG, IgM ELISAs, conventional PCR (cPCR), and real-time PCR (rtPCR) for early detection of human leptospirosis. Overall accuracy of IgM ELISA was sensitivity of 87.9%, specificity of 97.0%, and area under the curve of 0.940. When the 4 methods were compared, IgM ELISA showed the greatest diagnostic accuracy (J=0.6) followed by rtPCR (J=0.4), cPCR (J=0.2) and IgG ELISA (J=0.1). Our results support the use of IgM ELISA and rtPCR for early diagnosis of the disease. Moreover, due to their high specificity, they could be also useful to replace or supplement microscopic agglutination test as a confirmatory test, allowing more confirmations.

Chronic Chagas disease diagnosis relies on laboratory tests due to its clinical characteristics. The aim of this research was to review commercial enzyme-linked immunosorbent assay (ELISA) and polymerase chain reaction (PCR) diagnostic test performance. Performance of commercial ELISA or PCR for the diagnosis of chronic Chagas disease were systematically searched in PubMed, Scopus, Embase, ISI Web, and LILACS through the bibliography from 1980-2014 and by contact with the manufacturers. The risk of bias was assessed with QUADAS-2. Heterogeneity was estimated with the I2 statistic. Accuracies provided by the manufacturers usually overestimate the accuracy provided by academia. The risk of bias is high in most tests and in most QUADAS dimensions. Heterogeneity is high in either sensitivity, specificity, or both. The evidence regarding commercial ELISA and ELISA-rec sensitivity and specificity indicates that there is overestimation. The current recommendation to use two simultaneous serological tests can be supported by the risk of bias analysis and the amount of heterogeneity but not by the observed accuracies. The usefulness of PCR tests are debatable and health care providers should not order them on a routine basis. PCR may be used in selected cases due to its potential to detect seronegative subjects. PMID:26814640

High density functionalization of DNA with ethynyl and octadiynyl side chains followed by CuAAC "click labeling" with 9-azidomethylanthracene was performed. Alkynyl DNA was also cross-linked with fluorogenic 9,10-bis-azidomethylanthracene employing the "bis-click" reaction. By this means the fluorescence of the anthracene moiety was imparted to the virtually nonfluorescent DNA. Phosphoramidites of 8-aza-7-deaza-2'-deoxyadenosine with short and long linker arms in a steric nondemanding 7-position were utilized in solid phase oligodeoxynucleotide synthesis. High density alkynylated DNA-without anthracene residues-was found to be of comparable stability with both long and short linker arms. High density anthracene functionalized DNA became less stable with the short linker compared to that with the long linker connectivity. Interstrand cross-linked homodimers constructed from alkynylated oligonucleotides with fluorogenic 9,10-bis-azidomethylanthracene were hybridized with complementary strands to form double helices. They are more stable when the linker was located at a terminus than in a central position. Short linker anthracene adducts were destabilizing compared to long linker adducts. The fluorogenic anthracene residues not only have a significant effect on the duplex stability, but also impart fluorescence to the species. Fluorescence of cross-linked double helices with long linker connectivity was quenched when the cross-link was in a terminal position and was dequenched when the linker was connecting the two double helices at the center of the molecule. The fluorescence of the anthracene cross-linked double helices was strongly increased (dequenched) when the correct base pair was formed, while no change occurred upon mismatch formation.

Cardiac amyloidosis represents an archetypal form of restrictive heart disease, characterized by profound diastolic dysfunction. As ejection fraction is preserved until the late stage of the disease, the majority of patients do fulfill the definition of diastolic heart failure, that is, heart failure with preserved ejection fraction (HFpEF). In another clinical model of HFpEF, that is, pressure-overload hypertrophy, depressed midwall fractional shortening (mFS) has been shown to be a powerful prognostic factor. To assess the potential prognostic role of mFS in cardiac light-chain amyloidosis with preserved ejection fraction, we enrolled 221 consecutive untreated patients, in whom a first diagnosis of cardiac light-chain amyloidosis was concluded between 2008 and 2010. HFpEF was present in 181 patients. Patients in whom cardiac involvement was excluded served as controls (n = 121). Prognosis was assessed after a median follow-up of 561 days. When compared with light-chain amyloidosis patients without myocardial involvement, cardiac light-chain amyloidosis was characterized by increased wall thickness (P chain amyloidosis with normal ejection fraction, depressed circumferential mFS, a marker of myocardial contractile dysfunction, is a powerful predictor of survival.

Full Text Available A central question in brain evolution is how species-typical behaviors, and the neural function-structure mappings supporting them, can be acquired and inherited. Advocates of brain modularity, in its different incarnations across scientific subfields, argue that natural selection must target domain-dedicated, separately modifiable neural subsystems, resulting in genetically-specified functional modules. In such modular systems, specification of neuron number and functional connectivity are necessarily linked. Mounting evidence, however, from allometric, developmental, comparative, systems-physiological, neuroimaging and neurological studies suggests that brain elements are used and reused in multiple functional systems. This variable allocation can be seen in short-term neuromodulation, in neuroplasticity over the lifespan and in response to damage. We argue that the same processes are evident in brain evolution. Natural selection must preserve behavioral functions that may co-locate in variable amounts with other functions. In genetics, the uses and problems of pleiotropy, the re-use of genes in multiple networks have been much discussed, but this issue has been sidestepped in neural systems by the invocation of modules. Here we highlight the interaction between evolutionary and developmental mechanisms to produce distributed and overlapping functional architectures in the brain. These adaptive mechanisms must be robust to perturbations that might disrupt critical information processing and action selection, but must also recognize useful new sources of information arising from internal genetic or environmental variability, when those appear. These contrasting properties of robustness and evolvability have been discussed for the basic organization of body plan and fundamental cell physiology. Here we extend them to the evolution and development, evo-devo, of brain structure.

Polyhydroxyalkanoates (PHAs) are biodegradable biocompatible polyesters, which accumulate as granules in the cytoplasm of many bacteria under unbalanced growth conditions. Medium-chain-length PHAs (mcl-PHAs), characterized by C6-C14 branched monomer chains and typically produced by Pseudomonas species, are promising thermoelastomers, as they can be further modified by introducing functional groups in the side chains. Functionalized PHAs are obtained either by feeding structurally related substrates processed through the beta-oxidation pathway, or using specific strains able to transform sugars or glycerol into unsaturated PHA by de novo fatty-acid biosynthesis. Functionalized mcl-PHAs provide modified mechanical and thermal properties, and consequently have new processing requirements and highly diverse potential applications in emergent fields such as biomedicine. However, process development and sample availability are limited due to the toxicity of some precursors and still low productivity, which hinder investigation. Conversely, improved mutant strains designed through systems biology approaches and cofeeding with low-cost substrates may contribute to the widespread application of these biopolymers. This review focuses on recent developments in the production of functionalized mcl-PHAs, placing particular emphasis on strain and bioprocess design for cost-effective production.

Genomic islands have been shown to harbor functional traits that differentiate ecologically distinct populations of environmental bacteria. A comparative analysis of the complete genome sequences of the marine Actinobacteria Salinispora tropica and Salinispora arenicola reveals that 75% of the species-specific genes are located in 21 genomic islands. These islands are enriched in genes associated with secondary metabolite biosynthesis providing evidence that secondary metabolism is linked to functional adaptation. Secondary metabolism accounts for 8.8% and 10.9% of the genes in the S. tropica and S. arenicola genomes, respectively, and represents the major functional category of annotated genes that differentiates the two species. Genomic islands harbor all 25 of the species-specific biosynthetic pathways, the majority of which occur in S. arenicola and may contribute to the cosmopolitan distribution of this species. Genome evolution is dominated by gene duplication and acquisition, which in the case of secondary metabolism provide immediate opportunities for the production of new bioactive products. Evidence that secondary metabolic pathways are exchanged horizontally, coupled with earlier evidence for fixation among globally distributed populations, supports a functional role and suggests that the acquisition of natural product biosynthetic gene clusters represents a previously unrecognized force driving bacterial diversification. Species-specific differences observed in clustered regularly interspaced short palindromic repeat sequences suggest that S. arenicola may possess a higher level of phage immunity, whereas a highly duplicated family of polymorphic membrane proteins provides evidence for a new mechanism of marine adaptation in Gram-positive bacteria.

The unsuccessful astronomical searches for some important astrophysical and astrobiological molecules have been linked to the large partition function of these molecules. This letter reports an extensive investigation of the relationship between partition function and astronomical observation of interstellar isomers using high level quantum chemical calculations. 120 molecules from 30 different isomeric groups have been considered. Partition function and thermodynamic stabilities are determined for each set of isomeric species. From the results, there is no direct correlation between partition function and astronomical observation of the same isomeric species. Though interstellar formations processes are generally controlled by factors like kinetics, thermodynamics, formation and destruction pathways. However, the observation of the isomers seems to correlate well with thermodynamics. For instance, in all the groups considered, the astronomically detected isomers are the thermodynamically most stable molecules in their respective isomeric groups. The implications of these results in accounting for the limited number of known cyclic interstellar molecules, unsuccessful searches for amino acid and the possible molecules for astronomical observations are discussed.

Full Text Available Transcranial focused ultrasound (FUS is capable of modulating the neural activity of specific brain regions, with a potential role as a non-invasive computer-to-brain interface (CBI. In conjunction with the use of brain-to-computer interface (BCI techniques that translate brain function to generate computer commands, we investigated the feasibility of using the FUS-based CBI to non-invasively establish a functionallink between the brains of different species (i.e. human and Sprague-Dawley rat, thus creating a brain-to-brain interface (BBI. The implementation was aimed to non-invasively translate the human volunteer's intention to stimulate a rat's brain motor area that is responsible for the tail movement. The volunteer initiated the intention by looking at a strobe light flicker on a computer display, and the degree of synchronization in the electroencephalographic steady-state-visual-evoked-potentials (SSVEP with respect to the strobe frequency was analyzed using a computer. Increased signal amplitude in the SSVEP, indicating the volunteer's intention, triggered the delivery of a burst-mode FUS (350 kHz ultrasound frequency, tone burst duration of 0.5 ms, pulse repetition frequency of 1 kHz, given for 300 msec duration to excite the motor area of an anesthetized rat transcranially. The successful excitation subsequently elicited the tail movement, which was detected by a motion sensor. The interface was achieved at 94.0±3.0% accuracy, with a time delay of 1.59±1.07 sec from the thought-initiation to the creation of the tail movement. Our results demonstrate the feasibility of a computer-mediated BBI that links central neural functions between two biological entities, which may confer unexplored opportunities in the study of neuroscience with potential implications for therapeutic applications.

Full Text Available The landscape of Mengsong, southwest China, was biologically diverse until recently due to historical biogeographical processes overlain by the swidden-cultivation practices of the Hani who migrated there several centuries ago. Our research sought to understand how the Hani adjusted their livelihoods to new policies, markets, and technologies, and the consequences for biodiversity conservation. We combined landscape, plot, and household surveys, interviews, and reviews of secondary documents, to reconstruct the major changes and responses to challenges in the social-ecological system over previous decades. Significant changes from closed to open canopy of secondary-forest vegetation took place between 1965-1993 and from open-canopy to closed-canopy forest between 1993-2006, mostly explainable by changes in state land-use policies and the market economy. Most remaining swidden-fallow succession had been converted into tea or rubber plantations. Swidden-fallow fields used to contain significant levels of biological diversity. Until 2000, biodiversity served several important ecological and social functions in the Hani livelihood system. Indigenous institutions were often functional, for example, linked to fire control, soil management, and watershed protection. For centuries, the Hani had detailed knowledge of the landscape, helping them to adjust rapidly to ecological disturbances and changes in production demands. The Hani understood succession processes that enabled them to carry out long-term land-management strategies. Recent government policies and market dynamics have simplified livelihoods and landscapes, seriously reducing biodiversity, but greatly increasing the area of closed-canopy forest (including plantations and undermining the usefulness of Hani knowledge and land-use institutions. Meeting both conservation and development objectives in this landscape will require new functionallinks between sustainable livelihoods, culture, and

The structural similarity between defensins and scorpion neurotoxins suggests that they might have evolved from a common ancestor. However, there is no direct experimental evidence demonstrating a functionallink between scorpion neurotoxins and defensins. The scorpion defensin BmKDfsin4 from Mesobuthus martensiiKarsch contains 37 amino acid residues and a conserved cystine-stabilized α/β structural fold. The recombinant BmKDfsin4, a classical defensin, has been found to have inhibitory activity against Gram-positive bacteria such as Staphylococcus aureus, Bacillus subtilis, and Micrococcus luteusas well as methicillin-resistant Staphylococcus aureus Interestingly, electrophysiological experiments showed that BmKDfsin4,like scorpion potassium channel neurotoxins, could effectively inhibit Kv1.1, Kv1.2, and Kv1.3 channel currents, and its IC50value for the Kv1.3 channel was 510.2 nm Similar to the structure-function relationships of classical scorpion potassium channel-blocking toxins, basic residues (Lys-13 and Arg-19) of BmKDfsin4 play critical roles in peptide-Kv1.3 channel interactions. Furthermore, mutagenesis and electrophysiological experiments demonstrated that the channel extracellular pore region is the binding site of BmKDfsin4, indicating that BmKDfsin4 adopts the same mechanism for blocking potassium channel currents as classical scorpion toxins. Taken together, our work identifies scorpion BmKDfsin4 as the first invertebrate defensin to block potassium channels. These findings not only demonstrate that defensins from invertebrate animals are a novel type of potassium channel blockers but also provide evidence of a functionallink between defensins and neurotoxins.

In pedestrian detection methods, their high accuracy detection rates are always obtained at the cost of a large amount of false pedestrians. In order to overcome this problem, the authors propose an accurate pedestrian detection system based on two machine learning methods: cascade AdaBoost detector and random vector functional-link net. During the offline training phase, the parameters of a cascade AdaBoost detector and random vector functional-link net are trained by standard dataset. These...

This paper addresses the problem of handling the uncertainty of demand in aone-supplier-one-retailer supply chain system. Demand variation often makes the real productiondifferent from what is originally planned, causing a deviation cost from the production plan. Assumethe market demand is sensitive to the retail price in a nonlinear form, we show how to effectivelyhandle the demand uncertainty in a supply chain, both for the case of centralized-decision-makingsystem and the case of decentralized-decision-making system with perfect coordination.

The excess Helmholtz free energy functional for nonpolar chain-like molecules is formulated in terms of a weighted density approximation (WDA) for short-range interactions and a Weaks-Chandler-Andersen (WCA) approximation and a Barker-Henderson (BH) theory for long-range attraction. Within the framework of density functional theory (DFT), vapour-liquid interfacial properties including density profile and surface tension, and vapour-liquid nucleation properties including density profile, work of formation and number of particles are investigated for spherical and chainlike molecules. The obtained vapour-liquid surface tension and the number of particles in critical nucleus for LennardJones (L J) fluids are consistent with the simulation results. The influences of supersaturation, temperature and chain length on vapour-liquid nucleation properties are discussed.

The cost-benefit analysis of data associated with re-processing of used products often involves the uncertainty feature of cash-flow modeling. The data is not objective because of uncertainties in supply, quality and disassembly times of used products. Hence, decision-makers must rely on "fuzzy" data for analysis. The same parties that are involved in the forward supply chain often carry out the collection and re-processing of used products. It is therefore important that the cost-benefit analysis takes the data of both new products and used products into account. In this paper, a fuzzy cost-benefit function is proposed that is used to perform a multi-criteria economic analysis to select the most economical products to process in a closed-loop supply chain. Application of the function is detailed through an illustrative example.

Human short-chain dehydrogenases/reductases (SDRs) protein family has been the subject of recent studies for its critical role in human metabolism. Studies also found that single nucleotide polymorphisms of the SDR protein family were responsible for a variety of genetic diseases, including type II diabetes. This study reports the effect of sequence variation on the structural and functional integrities of human SDR protein family using phylogenetics and correlated mutation analysis tools. Ou...

ENGLISH ABSTRACT: This paper discusses the results obtained from studies on different Rapid Tooling process chains in order to improve the design and manufacture of foundry equipment that is used for sand casting of prototypes in final material. These prototypes are intended for functional and pre-production tests of vehicles. The Three Dimensional Printing process is used as core technology. Subsequently, while considering aspects such as time, cost, quality (accuracy and surface ro...

Mixed-effect Markov chain models have been recently proposed to characterize the time course of transition probabilities between sleep stages in insomniac patients. The most recent one, based on multinomial logistic functions, was used as a base to develop a final model combining the strengths of the existing ones. This final model was validated on placebo data applying also new diagnostic methods and then used for the inclusion of potential age, gender, and BMI effects. Internal validation w...

Linking competitive outcomes to environmental conditions is necessary for understanding species' distributions and responses to environmental change. Despite this importance, generalizable approaches for predicting competitive outcomes across abiotic gradients are lacking, driven largely by the highly complex and context-dependent nature of biotic interactions. Here, we present and empirically test a novel niche model that uses functional traits to model the niche space of organisms and predict competitive outcomes of co-occurring populations across multiple resource gradients. The model makes no assumptions about the underlying mode of competition and instead applies to those settings where relative competitive ability across environments correlates with a quantifiable performance metric. To test the model, a series of controlled microcosm experiments were conducted using genetically related strains of a widespread microbe. The model identified trait microevolution and performance differences among strains, with the predicted competitive ability of each organism mapped across a two-dimensional carbon and nitrogen resource space. Areas of coexistence and competitive dominance between strains were identified,and the predicted competitive outcomes were validated in approximately 95% of the pairings. By linking trait variation to competitive ability, our work demonstrates a generalizable approach for predicting and modelling competitive outcomes across changing environmental contexts.

Understanding mechanisms of soil carbon (C) turnover requires understanding the link between microbial community dynamics and soil decomposition processes. We present here an individual-based model that aims at elucidating this link by a bottom-up approach. Our approach differs from traditional soil C cycling models in that the overall dynamics of soil organic matter turnover emerges as the result of interactions between individual microbes at the soil microsite level, rather than being described by stock and flow rate equations at the bulk soil level. All soil microbes are modeled individually, each belonging to one of several functional groups defined by functional traits. Specifically, functional traits determine (1) growth and turnover rates, (2) production of extracellular enzymes and (3) microbial cell stoichiometry. Our model incorporates competition for space and nutrients (C and nitrogen, N) as well as synergistic interactions between individual microbes in a spatially structured environment represented by a two-dimensional grid. Due to different C and N limitations of different functional groups, community composition is sensitive to the availability of complex and labile C and N. Thus, altered resource availability changes microbial community composition, which in turn affects CO2 and N release from the soil. In our model, microbes constantly alter their own environment through the decomposition of different substrates, thereby exerting a feedback on community composition, which leads to a succession of microbial groups. We used the model's intrinsic link between resource availability, community dynamics and decomposition function to investigate the mechanism underlying the rhizosphere priming effect (i.e. increased decomposition of older soil C triggered by the input of labile C). In particular, we examined the spatial growth of a root releasing exudates of varying C:N ratios under the presence or absence of different functional groups. We find that a

The reverse supply chain (RSC) contains inherent uncertainties, e.g. the quality level and return volume of used products. By contrast, the catalyst manufacturing industry is characterized by Certainty (manifested in e.g. well-defined and highly controlled production – processes and widespread...

textabstractBackground: Evidence is accumulating that a dietary supply of long-chain polyunsaturated fatty acids (LC-PUFAs) enhances the development of attention and efficient information processing in infants. However, it is uncertain whether LC-PUFAs in infancy influence cognitive development in l

The phase behaviour of a microemulsion system consisting of equal volumes of brine and oil, sodium dodecyl sulphate (SDS) as surfactant and alcohols of different chain lengths (pentanol, hexanol and heptanol) as cosurfactant was studied. In the case of pentanol, at low surfactant concentrations and

A practical method was developed for the preparation of a diastereomeric library of C2-symmetric chiral 4-pyrrolidinopyridine catalysts with dual amide side chains. Use of a racemic precursor is the key to the concise production of catalysts with diverse stereochemisty.

The phase behaviour of a microemulsion system consisting of equal volumes of brine and oil, sodium dodecyl sulphate (SDS) as surfactant and alcohols of different chain lengths (pentanol, hexanol and heptanol) as cosurfactant was studied. In the case of pentanol, at low surfactant concentrations and

Full Text Available The close association between executive functions (EFs and educational achievement has led to the idea that targeted EF training might facilitate learning and goal-directed behavior in the classroom. The evidence that training interventions have long-lasting and transferable effects is however decidedly mixed (Melby-Lervåg and Hulme, 2013; Simons et al., 2016. The goal of the current paper is to propose a new CanDiD framework for re-thinking EF and its links to education. Based on findings from basic EF research, the proposed CanDiD framework highlights dynamic and contextual influences on EF and emphasizes the importance of development and individual differences for understanding these effects. Implications for remedial interventions and curriculum design are discussed.

Minorities in the United States have well-documented health disparities. Cultural barriers and biases by health care providers may contribute to lower quality of services which may contribute to these disparities. However, evidence linking cultural competency and health outcomes is lacking. This study, part of an ongoing quality improvement effort, tested the mediation hypothesis that patients' perception of provider cultural competency indirectly influences patients' health outcomes through process of care. Data were from patient satisfaction surveys collected in seven mental health clinics (n=94 minority patients). Consistent with our hypothesis, patients' perception of clinicians' cultural competency was indirectly associated with patients' self-reported improvements in social interactions, improvements in performance at work or school, and improvements in managing life problems through the patients' experience of respect, trust, and communication with the clinician. These findings indicate that process of care characteristics during the clinical encounter influence patients' perceptions of clinicians' cultural competency and affect functional outcomes.

Among mental disorders, mental retardation has been shown to be caused by various factors including a large array of genetic mutations. On the basis of remarkable progress, the emerging view is that defects in the regulation of synaptic activity and morphogenesis of dendritic spines are apparently common features associated with mutations in several genes implicated in mental retardation. In this review, we will discuss X-linked MR-related gene products that are potentially involved in the normal structure and function of the synapses, with a particular focus on pre- and/or post-synaptic plasticity mechanisms. Progress in understanding the underlying conditions leading to mental retardation will undoubtedly be gained from a closer collaboration of geneticists, physiologists and cognitive neuroscientists, which should enable the establishment of standardized approaches.

Full Text Available Skeletal muscle mass and function are progressively lost with age, a condition referred to as sarcopenia. By the age of 60, many older adults begin to be affected by muscle loss. There is a link between decreased muscle mass and strength and adverse health outcomes such as obesity, diabetes and cardiovascular disease. Data suggest that increasing dietary protein intake at meals may counterbalance muscle loss in older individuals due to the increased availability of amino acids, which stimulate muscle protein synthesis by activating the mammalian target of rapamycin (mTORC1. Increased muscle protein synthesis can lead to increased muscle mass, strength and function over time. This review aims to address the current recommended dietary allowance (RDA for protein and whether or not this value meets the needs for older adults based upon current scientific evidence. The current RDA for protein is 0.8 g/kg body weight/day. However, literature suggests that consuming protein in amounts greater than the RDA can improve muscle mass, strength and function in older adults.

Truncated linear models based on constrained and unconstrained mode expansions for a flexible link with torque actuation at its hub led us to examine the behavior of the open-loop-zeros of five commonly used SISO transfer functions. We arrive at new conclusions with regard to minimum- and non-minimum-phase zeros, and passivity of the transfer functions. The flexible-to-rigid inertia (FRI) ratio plays an important role in the determination of these characteristics. This paper illustrates how the zero locations of some of the transfer functions are dramatically affected by the FRI ratio. We also investigate the performance of a hub angle, hub rate, and relative tip position static feedback controller based on a reduced-order constrained mode model when applied to both unconstrained and constrained mode models of the same dimension. Simulations indicate that the constrained model can be stable while the unconstrained model is not for high FRI ratios. Our findings can provide useful information to designers in cases where the controller is sensitive to the 1ocation of the plant's zeros.

Full Text Available Purpose. To report a comparative prospective long-term functional analysis after Riboflavin UV A corneal cross-linking (CXL in three different age groups of patients affected by progressive keratoconus (KC. Methods. Functional analysis comprised paediatric patients (≤18 years included 152 eyes (29.5%; intermediate group (19–26 years 286 eyes (55.4%, and adults (≥27 years 78 eyes (15.1%. CXL was performed according to the Siena protocol by using the Vega CBM (Caporossi-Baiocchi-Mazzotta X linker (CSO, Florence, Italy at Siena University by the same authors. Pre- and post-op examinations included UCVA, BSCVA, corneal topography, and surface aberrometry (CSO Eye Top, Florence, Italy, at 48 months followup. Results. At 48 months followup paediatrics, intermediate, and adult patients showed a mean gain in UCVA of +0.2, +0.14 and +0.12 Snellen lines. BSCVA gained by a mean of +0.21, +0.2, and +0.1 Snellen lines. Kmax was reduced by a mean value of −0.9 D, −0.6 D, and −0.5 D, respectively. Coma values improved by a mean of −0.45 μm, −0.91 μm, and −0.19 μm, respectively. Treatment ensured a long-term keratoconus stabilization in over 90% of treated patients. Conclusion. According to our long-term comparative results, epithelium-off Riboflavin UV A cross-linking should be the first choice therapy of progressive KC, particularly in paediatric age and patients under 26 years.

We previously discovered the correlation between light-induced chromophore color change of a photo-receptor membrane protein bacteriorhodopsin (bR) and its two-dimensional crystalline state in the membrane. To apply this phenomenon to a novel optical memory device, it is necessary that bR molecules are immobilized as maintaining their structure and functional properties. In this work, a poly(vinyl alcohol) (PVA) hydrogel with physical cross-linkages (hydrogen bonds between PVA chains) that resulted from repeated freezing-and-thawing (FT) cycles was used as an immobilization medium. To investigate the effects of physically cross-linked PVA gelation on the structure and function of bR in purple membranes (PMs), spectroscopic techniques were employed against PM/PVA immobilized samples prepared with different FT cycle numbers. Visible circular dichroism spectroscopy strongly suggested PM stacking during gelation. X-ray diffraction data also indicated the PM stacking as well as its native-like crystalline lattice even after gelation. Time-resolved absorption spectroscopy showed that bR photocycle behaviors in PM/PVA immobilized samples were almost identical to that in suspension. These results suggested that a physically cross-linked PVA hydrogel is appropriate for immobilizing membrane proteins in terms of maintaining their structure and functionality.

Electronic properties, such as HOMO and LUMO energies, band gaps, ionization potential (IP) and electron affinity (EA) of 2,7- and 3,6-linked carbazole trimers, two conjugated oligomers with different linkages of carbazole, were studied by the density functional theory with Becke-Lee-Young-Parr composite exchange correlation functional (B3LYP). The absorption spectra of these compounds were also investigated by time-dependent density functional theory (TD-DFT) with 6-31G* basis set. The calculated results indicated that the HOMO and LUMO of the 2,7- and 3,6-linked carbazole trimers are both slightly destabilized on going from methyl substitution to sec-butyl substitution. Both IP and EA exhibit their good hole-transporting but poor electron-accepting ability. The presence of alkyl groups on the nitrogen atoms does not affect the intra-chain electronic delocalization along the molecular frame. Thus no significant effect on the band gap and absorption spectra of compounds has been found.

Classical biogeographical observations tell us that ecosystems (vegetation and soils) strongly respond to climate variation in terms of their structure and function. On the other hand the influence of vegetation function on climate via exchange of matter and energy with the atmosphere has become evident in the last decades via observational and modeling studies. Recent continuous observations of this exchange of CO2, H2O and sensible heat within the global observation network FLUXNET have enabled us to quantify ecosystem function in response to large eco-climatological spatio-temporal variability of climate. We see that ecosystem function co-varies strongly with climate, but that climate alone does not suffice to explain the variation in total. Instead vegetation biophysical and structural parameters co-determine the exchange of carbon, water and energy between the ecosystem and the atmosphere. By combining ecosystem level observation and information of spatial meteorological and vegetation remote sensing covariates we can infer global patterns of ecosystem atmosphere fluxes and derive key ecosystem functional properties globally. While this approach is powerful and meteorological and vegetation structural predictors explain more than 70% of the spatial variation of monthly fluxes at FLUXNET sites, it ignores the effect of ecophysiological vegetation properties, which is expected from plant physiological leaf or whole-plant studies. Hence, future research has to more strongly link the organismic trait information with ecosystem functional properties. For this we propose a framework that involves 1) the correlation of community aggregated traits with flux-derived ecosystem properties across a range of ecosystems, 2) the up-scaling of vegetation traits using spatially distributed geo-ecological co-variates and the comparison with global ecosystem functional properties and their co-variation with climate, 3) the use of vegetation traits instead of vegetation classes

Full Text Available The study involved investigations on phase behavior and physicochemical characterization of microemulsions (MEs stabilized by mixture containing polysorbates (C12-C18 as surfactants and n-alkanols (C2-C6 as cosurfactant. Distribution coefficient and Gibbs free energy were also determined for systems containing Tween 20 as surfactant. ME having Tween 20 as surfactant and ethanol as cosurfactant was found to exhibit maximium ME region as well as water solubilization capacity (WSC. Values of both these parameters were found to decrease as chain length of surfactant increased in all cases of alkanols with exception of Tween 80. This could be attributed to unsaturated structure of Tween 80 which presumably caused folding of chain and lesser oil penetration. Furthermore, the transition of w/o MEs to o/w MEs via bicontinuous structure along the dilution line was confirmed by conductivity, viscosity and droplet size analysis.

It is widely known that branched chain amino acids (BCAA) are not only elementary components for building muscle tissue but also participate in increasing protein synthesis in animals and humans. BCAA (isoleucine, leucine and valine) regulate many key signaling pathways, the most classic of which is the activation of the mTOR signaling pathway. This signaling pathway connects many diverse physiological and metabolic roles. Recent years have witnessed many striking developments in determining ...

The phase behaviour of a microemulsion system consisting of equal volumes of brine and oil, sodium dodecyl sulphate (SDS) as surfactant and alcohols of different chain lengths (pentanol, hexanol and heptanol) as cosurfactant was studied. In the case of pentanol, at low surfactant concentrations and increasing alcohol concentration, the well-known progression of phase equilibria, Winsor I—Winsor III—Winsor II, was observed. The use of hexanol or heptanol as cosurfactant leads to rather differe...

We use the form factors of the quantum transfer matrix in the zero-temperature limit in order to study the two-point ground-state correlation functions of the XXZ chain in the antiferromagnetic massive regime. We obtain novel form factor series representations of the correlation functions which differ from those derived either from the q-vertex-operator approach or from the algebraic Bethe Ansatz approach to the usual transfer matrix. We advocate that our novel representations are numerically more efficient and allow for a straightforward calculation of the large-distance asymptotic behaviour of the two-point functions. Keeping control over the temperature corrections to the two-point functions we see that these are of order {T}∞ in the whole antiferromagnetic massive regime. The isotropic limit of our result yields a novel form factor series representation for the two-point correlation functions of the XXX chain at zero magnetic field. Dedicated to the memory of Petr Petrovich Kulish.

The electronic and optical properties of extended functionalized carbyne chains, polyynes and cumulenes, are investigated with the localized Hartree-Fock method, with conventional Kohn-Sham methods, and with the Hartree-Fock method. It is found that even for very long polyynes the carbon-carbon bond lengths within a polyyne alternate while for long cumulenes no carbon-carbon bond length alternation occurs. Polyynes exhibit a finite HOMO-LUMO gap even if they become very long while cumulenes are found to become metallic in the limit of long chain lengths. The geometry and the electro-optical properties of polyynes cannot be influenced significantly by simple sp-{sigma}-bonded end groups. The optically active {sup 1}{sigma}{sub u}{sup +} functional theory (TDDFT). The known systematic underestimation of excitation energies in large chain-like systems by TDDFT methods is also found for the systems considered here. Deficiencies in the commonly used exchange-correlation kernels are identified as the main source of this shortcoming of TDDFT methods. Unphysical Coulomb self-interactions present in conventional Kohn-Sham potentials seem to not contribute significantly to the problem.

Automated assignment of protein function has received considerable attention in recent years for genome-wide study. With the rapid accumulation of genome sequencing data produced by high-throughput experimental techniques, the process of manually predicting functional properties of proteins has become increasingly cumbersome. Such large genomics data sets can only be annotated computationally. However, automated assignment of functions to unknown protein is challenging due to its inherent difficulty and complexity. Previous studies have revealed that solving problems involving complicated objects with multiple semantic meanings using the multi-instance multi-label (MIML) framework is effective. For the protein function prediction problems, each protein object in nature may associate with distinct structural units (instances) and multiple functional properties (class labels) where each unit is described by an instance and each functional property is considered as a class label. Thus, it is convenient and natural to tackle the protein function prediction problem by using the MIML framework. In this paper, we propose a sparse Markov chain-based semi-supervised MIML method, called Sparse-Markov. A sparse transductive probability graph is constructed to encode the affinity information of the data based on ensemble of Hausdorff distance metrics. Our goal is to exploit the affinity between protein objects in the sparse transductive probability graph to seek a sparse steady state probability of the Markov chain model to do protein function prediction, such that two proteins are given similar functional labels if they are close to each other in terms of an ensemble Hausdorff distance in the graph. Experimental results on seven real-world organism data sets covering three biological domains show that our proposed Sparse-Markov method is able to achieve better performance than four state-of-the-art MIML learning algorithms.

In this study we employed joint independent component analysis (jICA) to perform a novel multivariate integration of magnetoencephalography (MEG) and diffusion tensor imaging (DTI) data to investigate the link between function and structure. This model-free approach allows one to identify covariation across modalities with different temporal and spatial scales [temporal variation in MEG and spatial variation in fractional anisotropy (FA) maps]. Healthy controls (HC) and patients with schizophrenia (SP) participated in an auditory/visual multisensory integration paradigm to probe cortical connectivity in schizophrenia. To allow direct comparisons across participants and groups, the MEG data were registered to an average head position and regional waveforms were obtained by calculating the local field power of the planar gradiometers. Diffusion tensor images obtained in the same individuals were preprocessed to provide FA maps for each participant. The MEG/FA data were then integrated using the jICA software (http://mialab.mrn.org/software/fit). We identified MEG/FA components that demonstrated significantly different (p<0.05) covariation in MEG/FA data between diagnostic groups (SP vs. HC) and three components that captured the predominant sensory responses in the MEG data. Lower FA values in bilateral posterior parietal regions, which include anterior/posterior association tracts, were associated with reduced MEG amplitude (120-170 ms) of the visual response in occipital sensors in SP relative to HC. Additionally, increased FA in a right medial frontal region was linked with larger amplitude late MEG activity (300-400 ms) in bilateral central channels for SP relative to HC. Step-wise linear regression provided evidence that right temporal, occipital and late central components were significant predictors of reaction time and cognitive performance based on the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) cognitive assessment

X-linked mental retardation (XLMR) is an inherited disorder that mostly affects males and is caused by mutations in genes located on the X chromosome. Here, we show that the XLMR protein PHF8 and a C. elegans homolog F29B9.2 catalyze demethylation of di- and monomethylated lysine 9 of histone H3 (H......3K9me2/me1). The PHD domain of PHF8 binds to H3K4me3 and colocalizes with H3K4me3 at transcription initiation sites. Furthermore, PHF8 interacts with another XMLR protein, ZNF711, which binds to a subset of PHF8 target genes, including the XLMR gene JARID1C. Of interest, the C. elegans PHF8 homolog...... is highly expressed in neurons, and mutant animals show impaired locomotion. Taken together, our results functionallylink the XLMR gene PHF8 to two other XLMR genes, ZNF711 and JARID1C, indicating that MR genes may be functionallylinked in pathways, causing the complex phenotypes observed in patients...

The tunneling magnetoresistance (TMR) of a silicon chain sandwiched between nickel electrodes was examined by using first-principles density functional theory. The relative orientation of the magnetization in a parallel-alignment (PA) configuration of two nickel electrodes enhanced the current with a bias less than 0.4 V compared with that in an antiparallel-alignment configuration. Consequently, the silicon chain-nickel electrodes yielded good TMR characteristics. In addition, there was polarized spin current in the PA configuration. The spin polarization of sulfur atoms functioning as a linking bridge between the chain and nickel electrode played an important role in the magnetic effects of the electric current. Moreover, the hybridization of the sulfur 3p orbital and σ-conjugated silicon 3p orbital contributed to increasing the total current.

X-linked agammaglobulinemia (XLA) is an inherited immunodeficiency that results from mutations within the gene encoding Bruton’s tyrosine kinase (BTK). Many XLA-associated mutations affect splicing of BTK pre-mRNA and severely impair B cell development. Here, we assessed the potential of antisense, splice-correcting oligonucleotides (SCOs) targeting mutated BTK transcripts for treating XLA. Both the SCO structural design and chemical properties were optimized using 2′-O-methyl, locked nucleic acid, or phosphorodiamidate morpholino backbones. In order to have access to an animal model of XLA, we engineered a transgenic mouse that harbors a BAC with an authentic, mutated, splice-defective human BTK gene. BTK transgenic mice were bred onto a Btk knockout background to avoid interference of the orthologous mouse protein. Using this model, we determined that BTK-specific SCOs are able to correct aberrantly spliced BTK in B lymphocytes, including pro–B cells. Correction of BTK mRNA restored expression of functional protein, as shown both by enhanced lymphocyte survival and reestablished BTK activation upon B cell receptor stimulation. Furthermore, SCO treatment corrected splicing and restored BTK expression in primary cells from patients with XLA. Together, our data demonstrate that SCOs can restore BTK function and that BTK-targeting SCOs have potential as personalized medicine in patients with XLA. PMID:25105368

Decomposition is a critical source of plant nutrients, and drives the largest flux of terrestrial C to the atmosphere. Decomposing soil organic matter typically contains litter from multiple plant species, yet we lack a mechanistic understanding of how species diversity influences decomposition processes. Here, we show that soil C and N cycling during decomposition are controlled by the composition and diversity of chemical compounds within plant litter mixtures, rather than by simple metrics of plant species diversity. We amended native soils with litter mixtures containing up to 4 alpine plant species, and we used 9 litter chemical traits to evaluate the chemical composition (i.e., the identity and quantity of compounds) and chemical diversity of the litter mixtures. The chemical composition of the litter mixtures was the strongest predictor of soil respiration, net N mineralization, and microbial biomass N. Soil respiration and net N mineralization rates were also significantly correlated with the chemical diversity of the litter mixtures. In contrast, soil C and N cycling rates were poorly correlated with plant species richness, and there was no relationship between species richness and the chemical diversity of the litter mixtures. These results indicate that the composition and diversity of chemical compounds in litter are potentially important functional traits affecting decomposition, and simple metrics like plant species richness may fail to capture variation in these traits. Litter chemical traits therefore provide a mechanistic link between organisms, species diversity, and key components of below-ground ecosystem function.

Reports of early parenting were assessed using two measures, the Parental Bonding Index (PBI) and the Measure of Parenting Style (MOPS), in a sample of 265 patients with DSM-defined major depressive disorder. Psychiatrists then rated the extent to which sample members evidenced the personality "styles" underpinning 15 separate personality disorders, returning personality vignette scores. The extent of disordered functioning was also assessed across "parameters" and "domains" by psychiatrists, referrers, and family members, using a range of measures. Those with higher scores on vignettes measuring borderline, anxious, depressive, and self-defeating personality style rated parents as uncaring, overcontrolling, and abusive. When vignettes were consolidated into scores akin to the DSM clusters, the most consistent links between perceived dysfunctional parenting were with the Cluster C (anxious), and Cluster B (dramatic) styles and were nonsignificant for Cluster A (eccentric) style. Meeting criteria for an increasing number of personality disorder clusters was associated with increasing levels of adverse parenting. Multiple regression analyses indicated that disordered functioning (as assessed by the three independent rater groups) was most distinctly associated with paternal indifference and maternal overcontrol.

Full Text Available In practical active noise control (ANC systems, the primary path and the secondary path may be nonlinear and time-varying. It has been reported that the linear techniques used to control such ANC systems exhibit degradation in performance. In addition, the actuators of an ANC system very often have nonminimum-phase response. A linear controller under such situations yields poor performance. A novel functionallink artificial neural network (FLANN-based simultaneous perturbation stochastic approximation (SPSA algorithm, which functions as a nonlinear mode-free (MF controller, is proposed in this paper. Computer simulations have been carried out to demonstrate that the proposed algorithm outperforms the standard filtered-x least mean square (FXLMS algorithm, and performs better than the recently proposed filtered-s least mean square (FSLMS algorithm when the secondary path is time-varying. This observation implies that the SPSA-based MF controller can eliminate the need of the modeling of the secondary path for the ANC system.

Full Text Available Adolescents’ somatisation (i.e., the psychological tendency to experience and report multiple physical complaints for which no definite medical cause can be found; SOM and functional impairment (i.e., all bothersome aftermath of somatisation; FI were studied in relation to mothers’ protection, encouraging/monitoring, and minimisation of physical functional complaints. Besides main effects, interaction effects with other child and parenting characteristics were examined. A total of 990 adolescents and their mothers filled out questionnaires when the adolescents were respectively 12–13 (T1 and 13–14 (T2 years old. At T1, there was a significant relation between mothers’ higher amounts of minimisation and adolescents’ higher levels of SOM. Further, the link between mothers’ higher levels of T1 minimisation and adolescents’ higher amounts of T1 FI was significant, but not for adolescents with high levels of depressive mood. Longitudinal analyses revealed that mothers’ reactions did not significantly predict adolescents’ SOM/FI, nor did adolescents’ SOM/FI significantly predict mothers’ reactions. Practical implications are discussed.

X-linked agammaglobulinemia (XLA) is an inherited immunodeficiency that results from mutations within the gene encoding Bruton's tyrosine kinase (BTK). Many XLA-associated mutations affect splicing of BTK pre-mRNA and severely impair B cell development. Here, we assessed the potential of antisense, splice-correcting oligonucleotides (SCOs) targeting mutated BTK transcripts for treating XLA. Both the SCO structural design and chemical properties were optimized using 2'-O-methyl, locked nucleic acid, or phosphorodiamidate morpholino backbones. In order to have access to an animal model of XLA, we engineered a transgenic mouse that harbors a BAC with an authentic, mutated, splice-defective human BTK gene. BTK transgenic mice were bred onto a Btk knockout background to avoid interference of the orthologous mouse protein. Using this model, we determined that BTK-specific SCOs are able to correct aberrantly spliced BTK in B lymphocytes, including pro-B cells. Correction of BTK mRNA restored expression of functional protein, as shown both by enhanced lymphocyte survival and reestablished BTK activation upon B cell receptor stimulation. Furthermore, SCO treatment corrected splicing and restored BTK expression in primary cells from patients with XLA. Together, our data demonstrate that SCOs can restore BTK function and that BTK-targeting SCOs have potential as personalized medicine in patients with XLA.

Signal processing by means of analog circuits offers advantages from a power consumption viewpoint. Implementing wavelet transform (WT) using analog circuits is of great interest when low-power consumption becomes an important issue. In this article, a novel simple structure WT circuit in analog domain is presented by employing functionallink neural network (FLNN) and switched-current (SI) filters. First, the wavelet base is approximated using FLNN algorithms for giving a filter transfer function that is suitable for simple structure WT circuit implementation. Next, the WT circuit is constructed with the wavelet filter bank, whose impulse response is the approximated wavelet and its dilations. The filter design that follows is based on a follow-the-leader feedback (FLF) structure with multiple output bilinear SI integrators and current mirrors as the main building blocks. SI filter is well suited for this application since the dilation constant across different scales of the transform can be precisely implemented and controlled by the clock frequency of the circuit with the same system architecture. Finally, to illustrate the design procedure, a seventh-order FLNN-approximated Gaussian wavelet is implemented as an example. Simulations have successfully verified that the designed simple structure WT circuit has low sensitivity, low-power consumption and litter effect to the imperfections.

The ability to evaluate the balance between risk and reward and to adjust behavior accordingly is fundamental to adaptive decision-making. Although brain-imaging studies consistently have shown involvement of the dorsolateral prefrontal cortex, anterior insula and striatum during risky decision-making, activation in a neural network formed by these regions has not been linked to structural connectivity. Therefore, in this study, white-matter connectivity was measured with diffusion-weighted imaging in 40 healthy research participants who performed the Balloon Analogue Risk Task, a test of risky decision-making, during fMRI. Fractional anisotropy within a network that includes white-matter pathways connecting four regions (the prefrontal cortex, insula and midbrain to the striatum) was positively correlated with the number of risky choices and total amount earned on the task, and with the parametric modulation of activation in regions within the network to the level of risk during choice selection. Furthermore, analysis using a mixed model demonstrated how relationships of the parametric modulation of activation in each of the four aforementioned regions are related to risk probabilities, and how previous trial outcomes and task progression influence the choice to take risk. The present findings provide the first direct evidence that white-matter integrity is linked to function within previously identified components of a network that is activated during risky decision-making, and demonstrate that the integrity of white-matter tracts is critical in consolidating and processing signals between cortical and striatal circuits during the decision-making process.

The paper describes a clinical case of a female woman with nephropathy due to light chain deposition disease caused by secretion of κ Bence-Jones protein. Complete immunochemical remission was achieved after induction therapy using a bortezomib + cyclophosphamide + dexamethasone regimen. Renal function remained unchanged (glomerular filtration rate 16 ml/min), there was a reduction in proteinuria from 5.8 to 2.6 g/day. High-dose melphalan (200 mg/m2) chemotherapy with peripheral blood stem cell autotransplantation was performed as consolidation of remission. A year posttransplantation, there was no secretion of κ light chains; however, monoclonal IgG lambda emerged in a quantity of 3.2 g/l. At the same period, nephrotic syndrome became progressive (daily proteinuria 12 g) and dialysis-dependent renal failure developed. A repeat renal biopsy specimen revealed changes, suggesting that there was a decrease in renal deposits of κ light chains. Simultaneously with this, the obvious negative trend as progressive nephrosclerosis and fixation of IgG and λ light chains in the glomeruli (in the sclerotic areas) cause IgGλ monoclonal protein to be involved in the genesis of further kidney injury. Attention is also paid to different characteristics of capillary wall deposits by density (according to the electron microscopic findings), which may point to their different qualitative composition and possibly different formation duration. Papaprotein Gλ disappeared after a year without therapy, suggesting its reactivity. The findings confirm that worse renal function is caused by the action of paraprotein Gλ due to secondary (after autologous hematopoietic stem cells transplantation) monoclonal gammopathy.

Background: The spatiotemporal patterns of correlated neural activity during the transition from wakefulness to general anesthesia have not been fully characterized. Correlation analysis of blood-oxygen-level dependent (BOLD) functional magnetic resonance imaging (fMRI) allows segmentation of the brain into resting-state networks (RSNs), with functional connectivity referring to the covarying activity that suggests shared functional specialization. We quantified the persistence of these correlations following the induction of general anesthesia in healthy volunteers and assessed for a dynamic nature over time. Methods: We analyzed human fMRI data acquired at 0 and 1.2% vol sevoflurane. The covariance in the correlated activity among different brain regions was calculated over time using bounded Kalman filtering. These time series were then clustered into eight orthogonal motifs using a K-means algorithm, where the structure of correlated activity throughout the brain at any time is the weighted sum of all motifs. Results: Across time scales and under anesthesia, the reorganization of interactions between RSNs is related to the strength of dynamic connections between member pairs. The covariance of correlated activity between RSNs persists compared to that linking individual member pairs of different RSNs. Conclusions: Accounting for the spatiotemporal structure of correlated BOLD signals, anesthetic-induced loss of consciousness is mainly associated with the disruption of motifs with intermediate strength within and between members of different RSNs. In contrast, motifs with higher strength of connections, predominantly with regions-pairs from within-RSN interactions, are conserved among states of wakefulness and sevoflurane general anesthesia. PMID:28082871

The cytoskeleton of most eukaryotic cells is composed of three principal filamentous components: actin filaments, microtubules (MTs), and intermediate filaments. It is a highly dynamic system that plays crucial roles in a wide range of cellular processes, including migration, adhesion, cytokinesis, morphogenesis, intracellular traffic and signaling, and structural flexibility. Among the large number of cytoskeleton-associated proteins characterized to date, microtubule-actin cross-linking factor 1 (MACF1) is arguably the most versatile integrator and modulator of cytoskeleton-related processes. MACF1 belongs to the plakin family of proteins, and within it, to the spectraplakin subfamily. These proteins are characterized by the ability to bridge MT and actin cytoskeletal networks in a dynamic fashion, which underlies their involvement in the regulation of cell migration, axonal extension, and vesicular traffic. Studying MACF1 functions has provided insights not only into the regulation of the cytoskeleton but also into molecular mechanisms of both normal cellular physiology and cellular pathology. Multiple MACF1 isoforms exist, composed of a large variety of alternatively spliced domains. Each of these domains mediates a specific set of interactions and functions. These functions are manifested in tissue and cell-specific phenotypes observed in conditional MACF1 knockout mice. The conditional models described to date reveal critical roles of MACF1 in mammalian skin, nervous system, heart muscle, and intestinal epithelia. Complete elimination of MACF1 is early embryonic lethal, indicating an essential role for MACF1 in early development. Further studies of MACF1 domains and their interactions will likely reveal multiple new roles of this protein in various tissues.

Expression of nuclear angiotensin II type 1 (AT(1)) receptors in rat kidney provides further support for the concept of an intracellular renin-angiotensin system. Thus we examined the cellular distribution of renal ANG II receptors in sheep to determine the existence and functional roles of intracellular ANG receptors in higher order species. Receptor binding was performed using the nonselective ANG II antagonist (125)I-[Sar(1),Thr(8)]-ANG II ((125)I-sarthran) with the AT(1) antagonist losartan (LOS) or the AT(2) antagonist PD123319 (PD) in isolated nuclei (NUC) and plasma membrane (PM) fractions obtained by differential centrifugation or density gradient separation. In both fetal and adult sheep kidney, PD competed for the majority of cortical NUC (> or =70%) and PM (> or =80%) sites while LOS competition predominated in medullary NUC (> or =75%) and PM (> or =70%). Immunodetection with an AT(2) antibody revealed a single approximately 42-kDa band in both NUC and PM extracts, suggesting a mature molecular form of the NUC receptor. Autoradiography for receptor subtypes localized AT(2) in the tubulointerstitium, AT(1) in the medulla and vasa recta, and both AT(1) and AT(2) in glomeruli. Loading of NUC with the fluorescent nitric oxide (NO) detector DAF showed increased NO production with ANG II (1 nM), which was abolished by PD and N-nitro-l-arginine methyl ester, but not LOS. Our studies demonstrate ANG II receptor subtypes are differentially expressed in ovine kidney, while nuclear AT(2) receptors are functionallylinked to NO production. These findings provide further evidence of a functional intracellular renin-angiotensin system within the kidney, which may represent a therapeutic target for the regulation of blood pressure.

An alphaCD30xalphaCD16 bispecific monoclonal antibody (MAb) was previously shown to induce remission of Hodgkin's disease refractory to chemo- and radiotherapy through specific activation of natural killer (NK) cells, but the appearance of a human anti-mouse antibody (HAMA) response prevented its use for prolonged therapy. Here, we describe an effort to humanize the Fab arm directed against FcgammaRIII (CD16), which-in context with the previously humanized CD30 Fab fragment-provides the necessary component for the design of a clinically useful bispecific antibody. Thus, the CDRs of the anti-CD16 mouse IgG1/lambda MAb A9 were grafted onto human Ig sequences. In a first attempt, the murine V(lambda) domain was converted to a humanized lambda chain, which led, however, to complete loss of antigen-binding activity and extremely poor folding efficiency upon periplasmic expression in Escherichia coli. Hence, its CDRs were transplanted onto a human kappa light chain in a second attempt, which resulted in a functional recombinant Fab fragment, yet with 100-fold decreased antigen affinity. In the next step, an in vitro affinity maturation was performed, wherein random mutations were introduced into the humanized V(H) and V(kappa) domains through error-prone PCR, followed by a filter sandwich colony screening assay for increased binding activity towards the bacterially produced extracellular CD16 fragment. Finally, an optimized Fab fragment was obtained, which carries nine additional amino acid exchanges and exhibits an affinity that is within a factor of 2 identical to that of the original murine A9 Fab fragment. The resulting humanized Fab fragment was fully functional with respect to binding of the recombinant CD16 antigen in enzyme-linked immunosorbent assay and in cytofluorimetry with CD16-positive granulocytes, thus providing a promising starting point for the preparation of a fully human bispecific antibody that permits the therapeutic recruitment of NK cells.

Carbonic anhydrase (CA) is an ancient enzyme widespread among bacteria, archaea, and eukarya that catalyzes the following reaction: CO2 + H2O ⇌ HCO3- + H+. Its functions are critical for key cellular processes such as concentrating CO2 for autotrophic growth, pH regulation, and pathogen survival in hosts. Currently, there are six known CA classes (α, β, γ, δ, η, ζ) arising from several distinct evolutionary lineages. CA are widespread in sequenced genomes, with many organisms containing multiple classes of CA or multiple CA of the same class. Soils host rich microbial communities with diverse and important ecological functions, but the diversity and abundance of CA in soils has not been explored. CA appears to play an important, but poorly understood, role in some biogeochemical cycles such as those of CO2 and its oxygen isotope composition and also carbonyl sulfide (COS), which are potential tracers in predictive carbon cycle models. Recognizing the prevalence and functional significance of CA in soils, we used a combined bioinformatics and molecular biology approach to address fundamental questions regarding the abundance, diversity, and function of CA in soils. To characterize the abundance and diversity of the different CA classes in soils, we analyzed existing soil metagenomic and metatranscriptomic data from the DOE Joint Genome Institute databases. Out of the six classes of CA, we only found the α, β, and γ classes to be present in soils, with the β class being the most abundant. We also looked at genomes of sequenced soil microorganisms to learn what combination of CA classes they contain, from which we can begin to predict the physiological role of CA. To characterize the functional roles of the different CA classes in soils, we collected soil samples from a variety of biomes with diverse chemical and physical properties and quantified the rate of two CA-mediated processes: soil uptake of COS and acceleration of the oxygen isotope exchange

Full Text Available Nowadays, one cannot talk about an authentic rural tourism within a certain destination without emphasizing the local cultural heritage (cultural landscape, customs and traditions, gastronomy and so on. In the existing context, the local gastronomy is perceived as a marketing instrument efficient in differentiating the rural touristic destinations. A special place in the development of the traditional cuisine is represented by the setting up and the promotion of the short food supply chains which can be achieved by sustaining the small local producers and by putting into practice an environment-friendly traditional agriculture. Sustaining the partnerships between the owners of accommodation units and the small local agricultural producers represents an essential element in putting into practice a sustainable and qualitative rural tourism. Romania has a substantial potential as regards the enhancement of short food supply chains thanks to: the large number of semi-subsistence agricultural farms (with an area under 5 hectares, the „village-town connection” as regards the food procurement, especially from acquaintances and relatives and the carrying on of a traditional agriculture at a large scale in the rural households.The case studies emphasized in the current paper (Harghita and Neamţ Counties focus on the existence of short food supply chains, functional in the rural tourism sector under very different ways: touristic sheepfolds, trout farms, inns, authentic holiday villages, peasant guest houses etc.

Citrus leprosis virus C (CiLV-C) causes damage in citrus production in the South and Central America. Since closely related types of citrus viruses have recently been described monoclonal antibodies (MAbs) are needed for accurate and sensitive diagnosis of CiLV-C. In this study, MAbs to the expressed coat protein of CiLV-C were produced for serological detection of CiLV-C in crude extracts of infected tissues in double antibody sandwich enzyme-linked immunosorbent assays (DAS-ELISA), dot blot immunosorbent assays (DBIA) and immuonocapture-reverse transcription-polymerase chain reaction (IC-RT-PCR) procedures. Monoclonal antibodies were developed in mice to the purified expressed coat protein of CiLV-C. The published standard protocols of DAS-ELISA, DBIA and IC-RT-PCR were followed for the detection of coat protein p29 of CiLV-C in the crude extracts of CiLV-C infected tissues. Two monoclonal antibodies, designated G10 and C11, were identified from four potential candidates for the specific and sensitive detection of coat protein p29 of CiLV-C in the crude citrus extracts of CiLV-C infected tissues in DAS-ELISA, whereas G10 was also selected based on performance for use in the DBIA and IC-RT-PCR diagnostic assays. Sensitivity analysis comparing the three methods for detection of coat protein p29 of CiLV-C determined that IC-RT-PCR was more sensitive than DAS-ELISA and DBIA. The creation of MAbs to CiLV-C allows for the sensitive and accurate detection of the virus from CiLV-C infected citrus leaf tissues. Successful detection of the virus in three diagnostic assays formats provides flexibility to diagnosticians who can use either ELISA or DBIA for screening large numbers of samples, and IC-RT-PCR for rapid, sensitive confirmation testing. Published by Elsevier B.V.

In the nematode Caenorhabditis elegans, there exist two μ1 medium chains of the AP-1 clathrin-associated protein complex. Mutations of unc-101, the gene that encodes one of the μ1 chains, cause pleiotropic effects (Lee et al., 1994). In this report, we identified and analyzed the second μ1 chain gene, apm-1. Unlike the mammalian homologs, the two medium chains are expressed ubiquitously throughout development. RNA interference (RNAi) experiments with apm-1 showed that apm-1 and unc-101 were redundant in embryogenesis and in vulval development. Consistent with this, a hybrid protein containing APM-1, when overexpressed, rescued the phenotype of an unc-101 mutant. However, single disruptions of apm-1 or unc-101 have distinct phenotypes, indicating that the two medium chains may have distinct functions. RNAi of any one of the small or large chains of AP-1 complex (ς1, β1, or γ) showed a phenotype identical to that caused by the simultaneous disruption of unc-101 and apm-1, but not that by single disruption of either gene. This suggests that the two medium chains may share large and small chains in the AP-1 complexes. Thus, apm-1 and unc-101 encode two highly related μ1 chains that share redundant and distinct functions within AP-1 clathrin-associated protein complexes of the same tissue. PMID:10930467

The theory of string-like continuous curves and discrete chains have numerous important physical applications. Here we develop a general geometrical approach, to systematically derive Hamiltonian energy functions for these objects. In the case of continuous curves, we demand that the energy function must be invariant under local frame rotations, and it should also transform covariantly under reparametrizations of the curve. This leads us to consider energy functions that are constructed from the conserved quantities in the hierarchy of the integrable nonlinear Schr\\"odinger equation (NLSE). We point out the existence of a Weyl transformation that we utilize to introduce a dual hierarchy to the standard NLSE hierarchy. We propose that the dual hierarchy is also integrable, and we confirm this to the first non-trivial order. In the discrete case the requirement of reparametrization invariance is void. But the demand of invariance under local frame rotations prevails, and we utilize it to introduce a discrete va...

Full Text Available Consciousness is seen as a difficult binding problem. Binding, a process wheredifferent sensations evoked by an item are associated in the nervous system, can beviewed as a process similar to associative learning. Several reports that consciousness isassociated with some form of memory imply that different forms of memories have acommon feature contributing to consciousness. Based on a proposed synaptic mechanismcapable of explaining different forms of memory, we developed a framework forconsciousness. It is based on the formation of semblance of sensory stimulus from 1synaptic semblances when excitatory postsynaptic potentials arrive at functionallyLINKed postsynaptic membranes, and 2 network semblances when these potentialssummate to elicit action potential initiating activity in a network of neurons. It is thenpossible to derive a framework for consciousness as a multi-dimensional semblance.According to this framework, a continuum of semblances formed from backgroundsensory stimuli and oscillating neuronal activities serve to maintain consciousness.Feasibility of this framework to explain various physiological and pathological states ofconsciousness, its subjective nature and qualia is examined.

Evidence suggests that parenting attitudes are transmitted within families. However, limited research has examined this prospectively. The current prospective study examined direct effects of early maternal attitudes toward parenting (as measured at child age 4 by the Adult-Adolescent Parenting Inventory [AAPI]) on later youth parenting attitudes (as measured by the AAPI at youth age 18). Indirect effects via child maltreatment (physical abuse, sexual abuse, neglect, and emotional maltreatment), parent involvement, and youth functioning (internalizing and externalizing problems) were also assessed. Analyses were conducted on data from 412 families enrolled in the Longitudinal Studies of Child Abuse and Neglect (LONGSCAN). There were significant direct effects for three of the four classes of mother parenting attitudes (appropriate developmental expectations of children, empathy toward children, and appropriate family roles) on youth attitudes but not for rejection of punishment. In addition, the following indirect effects were obtained: Mother expectations influenced youth expectations via neglect; mother empathy influenced youth empathy via both parental involvement and youth externalizing problems; and mother rejection of punishment influenced youth rejection of punishment via youth internalizing problems. None of the child or family process variables, however, affected the link between mother and youth attitudes about roles.

Ensuring the optimum orientation, conformation, and density of substrate-bound antibodies is critical for the success of sandwich enzyme-linked immunosorbent assays (ELISAs). In this work, the authors utilize a diethylene glycol dimethyl ether plasma polymer (DGpp) coating, functionalized with chromium within a 96 well plate for the enhanced immobilization of a capture antibody. For an equivalent amount of bound antibody, a tenfold improvement in the ELISA signal intensity is obtained on the DGpp after incubation with chromium, indicative of improved orientation on this surface. Time-of-flight secondary-ion-mass-spectrometry (ToF-SIMS) and principal component analysis were used to probe the molecular species at the surface and showed ion fragments related to lysine, methionine, histidine, and arginine coupled to chromium indicating candidate antibody binding sites. A combined x-ray photoelectron spectroscopy and ToF-SIMS analysis provided a surface molecular characterization that demonstrates antibody binding via the chromium complex. The DGpp+Cr surface treatment holds great promise for improving the efficacy of ELISAs.

Integrin-linked kinase (ILK) is a phosphorylated protein that regulates physiological processes that overlap with those regulated by p21-activated kinase 1 (PAK1). Here we report the possible role of ILK phosphorylation by PAK1 in ILK-mediated signaling and intracellular translocation. We found that PAK1 phosphorylates ILK at threonine-173 and serine-246 in vitro and in vivo. Depletion of PAK1 decreased the levels of endogenous ILK phosphorylation in vivo. Mutation of PAK1 phosphorylation sites on ILK to alanine reduced cell motility and cell proliferation. Biochemical fractionation, confocal microscopy, and chromatin-interaction analyses of human cells revealed that ILK localizes predominantly in the cytoplasm but also resides in the nucleus. Transfection of MCF-7 cells with point mutants ILK-T173A, ILK-S246A, or ILK-T173A; S246A (ILK-DM) altered ILK localization. Selective depletion of PAK1 dramatically increased the nuclear and focal point accumulation of ILK, further demonstrating a role for PAK1 in ILK translocation. We also identified functional nuclear localization sequence and nuclear export sequence motifs in ILK, delineated an apparently integral role for ILK in maintaining normal nuclear integrity, and established that ILK interacts with the regulatory region of the CNKSR3 gene chromatin to negatively modulate its expression. Together, these results suggest that ILK is a PAK1 substrate, undergoes phosphorylation-dependent shuttling between the cell nucleus and cytoplasm, and interacts with gene-regulatory chromatin. PMID:17420447

The development of multicellular organisms requires integrin-mediated interactions between cells and their extracellular environment. Integrin binding to extracellular matrix catalyses assembly of multiprotein complexes, which transduce mechanical and chemical signals that regulate many aspects of cell physiology. Integrin-linked kinase (Ilk) is a multifunctional protein that binds beta-integrin cytoplasmic domains and regulates actin dynamics by recruiting actin binding regulatory proteins such as alpha- and beta-parvin. Ilk has also been shown to possess serine/threonine kinase activity and to phosphorylate signalling proteins such as Akt1 and glycogen synthase kinase 3beta (Gsk3beta) in mammalian cells; however, these functions have been shown by genetic studies not to occur in flies and worms. Here we show that mice carrying point mutations in the proposed autophosphorylation site of the putative kinase domain and in the pleckstrin homology domain are normal. In contrast, mice with point mutations in the conserved lysine residue of the potential ATP-binding site of the kinase domain, which mediates Ilk binding to alpha-parvin, die owing to renal agenesis. Similar renal defects occur in alpha-parvin-null mice. Thus, we provide genetic evidence that the kinase activity of Ilk is dispensable for mammalian development; however, an interaction between Ilk and alpha-parvin is critical for kidney development.

Translational informatics approaches are required for the integration of diverse and accumulating data to enable the administration of effective translational medicine specifically in complex diseases such as coronary artery disease (CAD). In the current study, a novel approach for elucidating the association between infection, inflammation and CAD was used. Genes for CAD were collected from the CAD‑gene database and those for infection and inflammation were collected from the UniProt database. The cytomegalovirus (CMV)‑induced genes were identified from the literature and the CAD‑associated clinical phenotypes were obtained from the Unified Medical Language System. A total of 55 gene ontologies (GO) termed functional communicator ontologies were identified in the gene sets linking clinical phenotypes in the diseasome network. The network topology analysis suggested that important functions including viral entry, cell adhesion, apoptosis, inflammatory and immune responses networked with clinical phenotypes. Microarray data was extracted from the Gene Expression Omnibus (dataset: GSE48060) for highly networked disease myocardial infarction. Further analysis of differentially expressed genes and their GO terms suggested that CMV infection may trigger a xenobiotic response, oxidative stress, inflammation and immune modulation. Notably, the current study identified γ‑glutamyl transferase (GGT)‑5 as a potential biomarker with an odds ratio of 1.947, which increased to 2.561 following the addition of CMV and CMV‑neutralizing antibody (CMV‑NA) titers. The C‑statistics increased from 0.530 for conventional risk factors (CRFs) to 0.711 for GGT in combination with the above mentioned infections and CRFs. Therefore, the translational informatics approach used in the current study identified a potential molecular mechanism for CMV infection in CAD, and a potential biomarker for risk prediction.

Our knowledge of the dynamics structuring microbial communities and the consequences this has for soil functions is rudimentary. In particular, predictions of the response of microbial communities to environmental change and the implications for associated ecosystem processes remain elusive. Understanding how environmental factors structure microbial communities and regulate the functions they perform is key to a mechanistic understanding of how biogeochemical cycles respond to environmental change. Soil salinization is an agricultural problem in many parts of the world. The activity of soil microorganisms is reduced in saline soils compared to non-saline soil. However, soil salinity often co-varies with other factors, making it difficult to assign responses of microbial communities to direct effects of salinity. A trait-based approach allows us to connect the environmental factor salinity with the responses of microbial community composition and functioning. Salinity along a salinity gradient serves as a filter for the community trait distribution of salt tolerance, selecting for higher salt tolerance at more saline sites. This trait-environment relationship can be used to predict responses of microbial communities to environmental change. Our aims were to (i) use salinity along natural salinity gradients as an environmental filter, and (ii) link the resulting filtered trait-distributions of the communities (the trait being salt tolerance) to the community composition. Soil samples were obtained from two replicated salinity gradients along an Australian salt lake, spanning a wide range of soil salinities (0.1 dS m-1 to >50 dS m-1). In one of the two gradients salinity was correlated with pH. Community trait distributions for salt tolerance were assessed by establishing dose-dependences for extracted bacterial communities using growth rate assays. In addition, functional parameters were measured along the salt gradients. Community composition of sites was compared

A straightforward explanation of fundamental tenets of quantum mechanics concerning the wave function results in the thesis that the quantum mechanical wave function is a link between human cognition and the physical world. The reticence on the part of physicists to adopt this thesis is discussed. A comparison is made to the behaviorists' consideration of mind, and the historical roots of how the problem concerning the quantum mechanical wave function arose are discussed. The basis for an empirical demonstration that the wave function is a link between human cognition and the physical world is provided through developing an experiment using methodology from psychology and physics. Based on research in psychology and physics that relied on this methodology, it is likely that Einstein, Podolsky, and Rosen's theoretical result that mutually exclusive wave functions can simultaneously apply to the same concrete physical circumstances can be implemented on an empirical level.

We study the properties of the generalized spin-1 Ising-Heisenberg model on a diamond chain, which can be considered as a theoretical model for the homometallic magnetic complex [Ni3(C4H2O4)2 -(μ3 - OH) 2(H2O)4 ] n ṡ(2H2 O) n. The model possesses a large variety of ground-state phases due to the presence of biquadratic and single-ion anisotropy parameters. Magnetization and quadrupole moment plateaus are observed at one- and two-thirds of the saturation value. The distributions of Yang-Lee and Fisher zeros are studied numerically for a variety of values of the model parameters. The usual value σ = -1/2 alongside an unusual value σ = -2/3 ​is determined for the Yang-Lee edge singularity exponents.

of enzymes involved in the 4th and 5th steps of GSL sugar chain elongation in vitro and explore the biological consequences of removing the enzymes involved in step 4 in vivo. Two beta4-N-Acetylgalactosyltransferase enzymes can carry out step 4 (beta4GalNAcTA and beta4GalNAcTB), and while they may have...... overlapping activity, the mutants produce distinct phenotypes. The beta4GalNAcTA mutant displays behavioral defects, which are also observed in viable brainiac mutants, suggesting that proper locomotion and coordination primarily depend on GSL elongation. beta4GalNAcTB mutant animal shows ventralization...... of ovarian follicle cells, which is caused by defective EGFR signaling between the oocyte and the dorsal follicle cells to specify dorsal fate. GSL sequentially elongated by Egh, Brn and beta4GalNAcTB in the oocyte contribute to this signaling pathway. Despite the similar enzymatic activity, we provide...

The inclusion complex formation of α-CD, β-CD, and γ-CD with various water-soluble polymers has been investigated, and the relationship between the chain cross-sectional areas of the polymers and the diameters of the cavities of cyclodextrins (molecular recognition) was found. Polyrotaxanes and tubular polymers were prepared on the basis of molecular recognition. Several kinds of polymers having tetraphenylporphyrin (TPP) and paramagnetic metallotetraphenylporphyrin (AgTPP, CuTPP, VOTPP or ZnTPP) have been prepared by radical polymerization of the corresponding monomers. Visible spectra of these polymers show hypochromism in the Soret bands of TPP moieties as compared with those of monomers. Polymer effects were observed in the magnetic behavior and oxygen adsorption of paramagnetic metallotetraphenylporphyrin moieties. Moreover, polymer effects on photophysical and photochemical behavior were found in the amphiphilic polymers covalently tethered with small amounts of zinc(Ⅱ)-tetraphenylporphyrin (ZnTPP).

The effect of low birth weight on children's development has been documented for a range of neurocognitive outcomes. However, few previous studies have examined the effect of birth weight variability within the normal range on children's neuropsychological development. The current study examined birth weight variation amongst children weighing ≥2500 g in relation to their language, executive functioning (EF), and theory of mind (ToM), and specified a developmental pathway in which birth weight was hypothesized to be associated with children's EF and ToM through their intermediary language skills. The current study used a prospective community birth cohort of 468 children. Families were recruited when children were newborns and followed up every 18 months until children were age 4.5. Language was assessed at age 3 using a standardized measure of receptive vocabulary (PPVT), and EF and ToM were measured at age 4.5 using previously validated and developmentally appropriate tasks. After controlling for potential confounding variables (family income, parent education, gestational age), birth weight within the normal range was associated with language ability at age 3 (β=.17; p=.012); and the effect of birth weight on both EF (z=2.09; p=.03) and ToM (z=2.07; p=.03) at age 4.5 operated indirectly through their language ability at age 3. Our findings indicate that the effects of birth weight on child neurocognition extend into the normal range of birth weight, and specific developmental mechanisms may link these skills over time.

A hallmark of atopic eczema (AE) is skin barrier dysfunction. Lipids in the stratum corneum (SC), primarily ceramides, fatty acids, and cholesterol, are crucial for the barrier function, but their role in relation to AE is indistinct. Filaggrin is an epithelial barrier protein with a central role in the pathogenesis of AE. Nevertheless, the precise causes of AE-associated barrier dysfunction are largely unknown. In this study, a comprehensive analysis of ceramide composition and lipid organization in nonlesional SC of AE patients and control subjects was performed by means of mass spectrometry, infrared spectroscopy, and X-ray diffraction. In addition, the skin barrier and clinical state of the disease were examined. The level of ceramides with an extreme short chain length is drastically increased in SC of AE patients, which leads to an aberrant lipid organization and a decreased skin barrier function. Changes in SC lipid properties correlate with disease severity but are independent of filaggrin mutations. We demonstrate for the first time that changes in ceramide chain length and lipid organization are directly correlated with the skin barrier defects in nonlesional skin of AE patients. We envisage that these insights will provide a new therapeutic entry in therapy and prevention of AE.

For the integrable higher-spin XXX and XXZ spin chains we present multiple-integral representations for the correlation function of an arbitrary product of Hermitian elementary matrices in the massless ground state. We give a formula expressing it by a single term of multiple integrals. In particular, we explicitly derive the emptiness formation probability (EFP). We assume 2s-strings for the ground-state solution of the Bethe-ansatz equations for the spin-s XXZ chain, and solve the integral equations for the spin-s Gaudin matrix. In terms of the XXZ coupling Δ we define ζ by Δ=cos ζ, and put it in a region 0⩽ζfunctions by the algebraic Bethe-ansatz, introducing the Hermitian elementary matrices in the massless regime, and taking advantage of the fusion construction of the R-matrix of the higher-spin representations of the affine quantum group.

Full Text Available The paradigm of chronobiology is based almost wholly upon the daily biological clock, or circadian rhythm, which has been the focus of intense molecular, cellular, pharmacological, and behavioral, research. However, the circadian rhythm does not explain biological timings related to fundamental aspects of life history such as rates of tissue/organ/body size development and control of the timing of life stages such as gestation length, age at maturity, and lifespan. This suggests that another biological timing mechanism is at work. Here we focus on a "many days" (multidien chronobiological period first observed as enigmatic recurring growth lines in developing mammalian tooth enamel that is strongly associate with all adult tissue, organ, and body masses as well as life history attributes such as gestation length, age at maturity, weaning, and lifespan, particularly among the well studied primates. Yet, knowledge of the biological factors regulating the patterning of mammalian life, such as the development of body size and life history structure, does not exist. To identify underlying molecular mechanisms we performed metabolome and genome analyses from blood plasma in domestic pigs. We show that blood plasma metabolites and small non-coding RNA (sncRNA drawn from 33 domestic pigs over a two-week period strongly oscillate on a 5-day multidien rhythm, as does the pig enamel rhythm. Metabolomics and genomics pathway analyses actually reveal two 5-day rhythms, one related to growth in which biological functions include cell proliferation, apoptosis, and transcription regulation/protein synthesis, and another 5-day rhythm related to degradative pathways that follows three days later. Our results provide experimental confirmation of a 5-day multidien rhythm in the domestic pig linking the periodic growth of enamel with oscillations of the metabolome and genome. This association reveals a new class of chronobiological rhythm and a snapshot of the

The paradigm of chronobiology is based almost wholly upon the daily biological clock, or circadian rhythm, which has been the focus of intense molecular, cellular, pharmacological, and behavioral, research. However, the circadian rhythm does not explain biological timings related to fundamental aspects of life history such as rates of tissue/organ/body size development and control of the timing of life stages such as gestation length, age at maturity, and lifespan. This suggests that another biological timing mechanism is at work. Here we focus on a "many days" (multidien) chronobiological period first observed as enigmatic recurring growth lines in developing mammalian tooth enamel that is strongly associate with all adult tissue, organ, and body masses as well as life history attributes such as gestation length, age at maturity, weaning, and lifespan, particularly among the well studied primates. Yet, knowledge of the biological factors regulating the patterning of mammalian life, such as the development of body size and life history structure, does not exist. To identify underlying molecular mechanisms we performed metabolome and genome analyses from blood plasma in domestic pigs. We show that blood plasma metabolites and small non-coding RNA (sncRNA) drawn from 33 domestic pigs over a two-week period strongly oscillate on a 5-day multidien rhythm, as does the pig enamel rhythm. Metabolomics and genomics pathway analyses actually reveal two 5-day rhythms, one related to growth in which biological functions include cell proliferation, apoptosis, and transcription regulation/protein synthesis, and another 5-day rhythm related to degradative pathways that follows three days later. Our results provide experimental confirmation of a 5-day multidien rhythm in the domestic pig linking the periodic growth of enamel with oscillations of the metabolome and genome. This association reveals a new class of chronobiological rhythm and a snapshot of the biological bases that

Objectives Both pre-frailty and frailty are linked with impaired executive function (EF) but the mechanism underlying this relationship is not known. Williams and colleagues’ model posits EF affects health outcomes via stress regulation. This model was utlized to test indicators of stress regulation as mediators of the relationship between EF and pre-frailty in older adults. Design Cross-sectional. Setting Academic general clinical research centers. Participants 690 community-dwelling older adults ≥ 50 years of age. Measurements Pre-frailty was measured using a modified form of the Fried Frailty measure. EF was assessed via telephone-based neurocognitive assessments. Indicators of stress regulation included: stress exposure (measured by perceived stress), reactivity and recovery (measured by heart rate) and restoration (measured by serum interleukin-6 and sleep quality). Results 396 individuals were classified as non-frail, 277 as pre-frail, and 17 as frail. Pre-frail and non-frail individuals were included in data analyses. Compared to non-frail individuals, prefrail were older and exhibited poorer EF, higher levels of stress exposure and poorer stress restoration. Poorer EF was associated with greater stress exposure, less stress reactivity, longer stress recovery and poorer stress restoration. The total effect of the relationship between EF and pre-frailty was significant with significant indirect effects supporting stress exposure and restoration as mediators of the relationship. Conclusion Stress exposure and restoration appear to mediate the relationship between EF and pre-frailty. Longitudinal studies are needed to clarify the direction of causality and determine whether stress regulation processes are appropriate targets for interventions aiming to prevent declines in EF and the development of pre-frailty. PMID:26412287

Full Text Available The short arms of the ten acrocentric human chromosomes share several repetitive DNAs, including ribosomal RNA genes (rDNA. The rDNA arrays correspond to nucleolar organizing regions that coalesce each cell cycle to form the nucleolus. Telomere disruption by expressing a mutant version of telomere binding protein TRF2 (dnTRF2 causes non-random acrocentric fusions, as well as large-scale nucleolar defects. The mechanisms responsible for acrocentric chromosome sensitivity to dysfunctional telomeres are unclear. In this study, we show that TRF2 normally associates with the nucleolus and rDNA. However, when telomeres are crippled by dnTRF2 or RNAi knockdown of TRF2, gross nucleolar and chromosomal changes occur. We used the controllable dnTRF2 system to precisely dissect the timing and progression of nucleolar and chromosomal instability induced by telomere dysfunction, demonstrating that nucleolar changes precede the DNA damage and morphological changes that occur at acrocentric short arms. The rDNA repeat arrays on the short arms decondense, and are coated by RNA polymerase I transcription binding factor UBF, physically linking acrocentrics to one another as they become fusogenic. These results highlight the importance of telomere function in nucleolar stability and structural integrity of acrocentric chromosomes, particularly the rDNA arrays. Telomeric stress is widely accepted to cause DNA damage at chromosome ends, but our findings suggest that it also disrupts chromosome structure beyond the telomere region, specifically within the rDNA arrays located on acrocentric chromosomes. These results have relevance for Robertsonian translocation formation in humans and mechanisms by which acrocentric-acrocentric fusions are promoted by DNA damage and repair.

The paradigm of chronobiology is based almost wholly upon the daily biological clock, or circadian rhythm, which has been the focus of intense molecular, cellular, pharmacological, and behavioral, research. However, the circadian rhythm does not explain biological timings related to fundamental aspects of life history such as rates of tissue/organ/body size development and control of the timing of life stages such as gestation length, age at maturity, and lifespan. This suggests that another biological timing mechanism is at work. Here we focus on a "many days" (multidien) chronobiological period first observed as enigmatic recurring growth lines in developing mammalian tooth enamel that is strongly associate with all adult tissue, organ, and body masses as well as life history attributes such as gestation length, age at maturity, weaning, and lifespan, particularly among the well studied primates. Yet, knowledge of the biological factors regulating the patterning of mammalian life, such as the development of body size and life history structure, does not exist. To identify underlying molecular mechanisms we performed metabolome and genome analyses from blood plasma in domestic pigs. We show that blood plasma metabolites and small non-coding RNA (sncRNA) drawn from 33 domestic pigs over a two-week period strongly oscillate on a 5-day multidien rhythm, as does the pig enamel rhythm. Metabolomics and genomics pathway analyses actually reveal two 5-day rhythms, one related to growth in which biological functions include cell proliferation, apoptosis, and transcription regulation/protein synthesis, and another 5-day rhythm related to degradative pathways that follows three days later. Our results provide experimental confirmation of a 5-day multidien rhythm in the domestic pig linking the periodic growth of enamel with oscillations of the metabolome and genome. This association reveals a new class of chronobiological rhythm and a snapshot of the biological bases that

Full Text Available We investigate a stochastic Food-Chain System dx(t=[r1(t-a11(tx-(a12(ty/(1+β1(tx+γ1(ty]xdt+σ1(txdB1(t, dy(t=[r2(t-a21(ty+(a22(tx/(1+β1(tx+γ1(ty-(a23(tz/(1+β2(ty+γ2(tz]ydt+σ2(tydB2(t, dz(t=[-r3(t+(a31(ty/(1+β2(ty+γ2(tz-a32(tz]zdt+σ3(tzdB3(t, where Bi(t, i = 1,2,3, is a standard Brownian motion. Firstly, the existence, the uniqueness, and the positivity of the solution are proved. Secondly, the stochastically ultimate boundedness of the system is investigated. Thirdly, the boundedness of moments and upper-growth rate of the solution are obtained. Then the global attractivity of the system is discussed. Finally, the main results are illustrated by several examples.

From recent findings about the indirect effect of metformin (MET) targeted on the respiratory chain complex I, we reconsidered this question and tried to determine the causality of any alteration at this enzymatic level using Xenopus laevis oocytes. Addition of MET (50 microM) reduced by 40% the rotenone-sensitive activity of complex I only in incubating intact oocytes but not in mitochondria isolated by differential centrifugation. The drug prior injected inside these cells had also no measurable effect. In spite of this and the weak binding of MET to the mitochondrial fraction, there was a fairly good correlation between the marked inhibitory action of MET on complex I and its progressive appearance within the oocyte cytoplasm. The intriguing observation that MET as a liposomal form was again able to exert its role when added directly to isolated mitochondria is in accordance with a membrane-mediated uptake and vesicular routing of MET. Furthermore, a temperature-dependent effect was clearly shown. At 4 degrees, oocytes failed to take up efficiently MET and accordingly its subsequent action on respiration was therefore lost. Likewise, MET transport was hindered and inhibition of complex I totally disappeared when a structural analog, asymmetrical dimethylarginine (ADMA), was placed together with MET either at an identical concentration or in excess. These data strongly support the view that MET may recognise some specific membranous sites, likely belonging to effector systems, before penetrating the cell in a bound state via an obscure endocytotic event which still has to be identified.

The purpose of this study was to specify the development of and links between executive functioning and theory of mind during middle childhood. One hundred four 7- to 12-year-old children completed a battery of age-appropriate tasks measuring working memory, inhibition, flexibility, theory of mind, and vocabulary. As expected, spatial working…

We used current knowledge of cellular processes involved in reductive dechlorination to develop a conceptual model to describe the regulatory system of dechlorination at the cell level; the model links bacterial growth and substrate consumption to the abundance of messenger RNA of functional gene...

Background: Cognitive processes and mechanisms underlying the strong link between attention-deficit/hyperactivity disorder (ADHD) and social problems remain unclear. Limited knowledge also exists regarding a subgroup of youth with ADHD who do not have social problems. This study investigated the extent to which executive function (EF) mediated the…

With reference to experimental data in the literature, we present a model consisting of two elastic elements, conceived to simulate resistance to stretching, at constant velocity of elongation, of corneal tissue affected by keratoconus, treated with riboflavin and ultraviolet irradiation to induce cross-linking. The function describing model behaviour adapted to stress and strain values. It was found that the Young's moduli of the two elastic elements increased in cross-linked tissues and that cross-linking treatment therefore increased corneal rigidity. It is recognized that this observation is substantially in line with the conclusion reported in the literature, obtained using an exponential fitting function. It is observed, however, that the latter function implies a condition of non-zero stresses without strain, and does not provide interpretative insights for lack of any biomechanical basis. Above all, the function fits a singular trend, inexplicably claimed to be viscoelastic, with surprising perfection. In any case, using the reported data, the study demonstrates that a fitting equation obtained by a modelling approach not only shows the evident efficacy of the treatment, but also provides orientations for studying modifications induced in cross-linked fibres.

The purpose of this study was to specify the development of and links between executive functioning and theory of mind during middle childhood. One hundred four 7- to 12-year-old children completed a battery of age-appropriate tasks measuring working memory, inhibition, flexibility, theory of mind, and vocabulary. As expected, spatial working…

The broader context of relational aggression in adolescent romantic relationships was assessed by considering the ways such aggression emerged from prior experiences of peer pressure and was linked to concurrent difficulties in psychosocial functioning. Longitudinal, multi-reporter data were obtained from 97 adolescents and their best friends at…

The broader context of relational aggression in adolescent romantic relationships was assessed by considering the ways such aggression emerged from prior experiences of peer pressure and was linked to concurrent difficulties in psychosocial functioning. Longitudinal, multi-reporter data were obtained from 97 adolescents and their best friends at…

Quantification and valuation of ecosystem services are critically dependent on the quality of underpinning science. While key ecological processes may be understood, translating this understanding into quantitative relationships suitable for use in an ecosystem services context remains challenging. Using blanket bogs as a case study, we derived quantitative 'pressure-response functions' linking anthropogenic pressures (drainage, burning, sulphur and nitrogen deposition) with ecosystem functio...

In recent years, an array of brain mapping techniques has been successfully employed to link individual differences in circuit function or structure in the living human brain with individual variations in the human genome. Several proof-of-principle studies provided converging evidence that brain...

This paper is concerned with the asymptotical behavior of solutions to the reaction-diffusion system under homogeneous Neumann boundary condition. By taking food ingestion and species' moving into account, the model is further coupled with Michaelis-Menten type functional response and nonlocal delay. Sufficient conditions are derived for the global stability of the positive steady state and the semitrivial steady state of the proposed problem by using the Lyapunov functional. Our results show...

In the X-linked form of chronic granulomatous disease (X91-degrees CGD), the genetic defect is linked to the CYBB locus on the X chromosome. We studied a family with a genetic defect in this gene, consisting of a G-->A substitution at the fifth base of the 5' donor splice site of intron 3. This muta

We investigated the hypothesis that exogenous collagen cross-linking can augment intact regions of tendon to mitigate mechanical propagation of partial tears. We first screened the low toxicity collagen cross-linkers genipin, methylglyoxal and ultra-violet (UV) light for their ability to augment tendon stiffness and failure load in rat tail tendon fascicles (RTTF). We then investigated cross-linking effects in load bearing equine superficial digital flexor tendons (SDFT). Data indicated that all three cross-linking agents augmented RTTF mechanical properties but reduced native viscoelasticity. In contrast to effects observed in fascicles, methylglyoxal treatment of SDFT detrimentally affected tendon mechanical integrity, and in the case of UV did not alter tendon mechanics. As in the RTTF experiments, genipin cross-linking of SDFT resulted in increased stiffness, higher failure loads and reduced viscoelasticity. Based on this result we assessed the efficacy of genipin in arresting tendon tear propagation in cyclic loading to failure. Genipin cross-linking secondary to a mid-substance biopsy-punch significantly reduced tissue strains, increased elastic modulus and increased resistance to fatigue failure. We conclude that genipin cross-linking of injured tendons holds potential for arresting tendon tear progression, and that implications of the treatment on matrix remodeling in living tendons should now be investigated.

A new method of image resolution up-conversion (image interpolation) based on maximum a posteriori sequence estimation is proposed. Instead of making a hard decision about the value of each missing pixel, we estimate the missing pixels in groups. At each missing pixel of the high resolution (HR) image, we consider an ensemble of candidate interpolation methods (interpolation functions). The interpolation functions are interpreted as states of a Markov model. In other words, the proposed method undergoes state transitions from one missing pixel position to the next. Accordingly, the interpolation problem is translated to the problem of estimating the optimal sequence of interpolation functions corresponding to the sequence of missing HR pixel positions. We derive a parameter-free probabilistic model for this to-be-estimated sequence of interpolation functions. Then, we solve the estimation problem using a trellis representation and the Viterbi algorithm. Using directional interpolation functions and sequence estimation techniques, we classify the new algorithm as an adaptive directional interpolation using soft-decision estimation techniques. Experimental results show that the proposed algorithm yields images with higher or comparable peak signal-to-noise ratios compared with some benchmark interpolation methods in the literature while being efficient in terms of implementation and complexity considerations.

Full Text Available This paper is concerned with the asymptotical behavior of solutions to the reaction-diffusion system under homogeneous Neumann boundary condition. By taking food ingestion and species' moving into account, the model is further coupled with Michaelis-Menten type functional response and nonlocal delay. Sufficient conditions are derived for the global stability of the positive steady state and the semitrivial steady state of the proposed problem by using the Lyapunov functional. Our results show that intraspecific competition benefits the coexistence of prey and predator. Furthermore, the introduction of Michaelis-Menten type functional response positively affects the coexistence of prey and predator, and the nonlocal delay is harmless for stabilities of all nonnegative steady states of the system. Numerical simulations are carried out to illustrate the main results.

population. A difference in the distribution of RBMY1 copy number was observed between the group with normal sperm motility and the group with asthenozoospermia. A positive correlation between the RBMY1 copy dosage and sperm motility was identified, and the males with fewer than six copies of RBMY1 showed an elevated risk for asthenozoospermia relative to those with six RBMY1 copies, the most common dosage in the population. The RBMY1 copy dosage was positively correlated with its mRNA and protein level in the testis. Sperm with high motility were found to carry more RBMY1 protein than those with relatively low motility. The RBMY1 protein was confirmed to predominantly localize in the neck and mid-piece region of sperm as well as the principal piece of the sperm tail. Our population study completes a chain of evidence suggesting that RBMY1 influences the susceptibility of males to asthenozoospermia by modulating sperm motility. High sequence similarity between the RBMY1 functional copies and a large number of pseudogenes potentially reduces the accuracy of the copy number detection. The mechanism underlying the CNV in RBMY1 is still unclear, and the effect of the structural variations in the RBMY1 copy cluster on the copy dosage of other protein-coding genes located in the region cannot be excluded, which may potentially bias our observations. Asthenozoospermia is a multi-factor complex disease with a limited number of proven susceptibility genes. This study identified a novel genomic candidate independently contributing to the condition, enriching our understanding of the role of AZF-linked genes in male reproduction. Our finding provides insight into the physiological and pathological characteristics of RBMY1 in terms of sperm motility, supplies persuasive evidence of the significance of RBMY1 copy number analysis in the clinical counselling of male infertility resulting from asthenozoospermia. This work was funded by the National Natural Science Foundation of China (Nos

Full Text Available Nada Andelic,1 Jan Borre Johansen,1 Erik Bautz-Holter,1,2 Anne Marit Mengshoel,3 Eva Bakke,3 Cecilie Roe1,21Department of Physical Medicine and Rehabilitation, Oslo University Hospital, Oslo, Norway; 2Faculty of Medicine, University of Oslo, Oslo, Norway; 3Department of Health Sciences, Institute of Health and Society, University of Oslo, Oslo, NorwayObjective: To describe commonly reported self-determined functional problems in patients with neck pain and to evaluate their fit to the components of the International Classification of Functioning, Disability, and Health (ICF.Methods: Overall, 249 patients were included in this cross-sectional study that comprised patients with neck pain referred to the outpatient clinic at Oslo University Hospital (2007–2009. Patients were asked to report their three most significant functional problems on the Patient-Specific Functional Scale, a self-determined measure of function. The ICF was used as a tool for analysis. Meaningful concepts within the functional problems were identified, coded, and linked to second-level categories within the components of “body functions,” and “activities and participation.” Two researchers performed coding and linking independently. The ICF categories were presented by percentage of the total number of functional problems linked to the ICF.Results: Of 628 reported functional problems, 13 meaningful ICF domains were identified: four domains belonging to the body functions component (b and nine domains belonging to activities and participation components (d. Within the 88 second-level ICF classification categories of body functions, the most frequently reported items were sleep function (b134; 27% and mobility of joint functions (b710; 26%. Within the 538 second-level categories of activities and participation, remunerative employment was reported as the most frequent item (d850; 15%, closely followed by doing housework (d640; 14%, and recreation and leisure

The clear and pressing need to reliably identify and predict shifts in plant phenology at landscape scales requires a critical link between mechanistic understanding of climate drivers and broad scale forecasts of plant responses to climate change. A multi-scale phenology study co-located with two eddy covariance towers was initiated on the Jornada Basin LTER in New Mexico in 2010 to bridge phenology patterns at the plant level with those representing aggregated signals at the landscape level. The study integrates phenology observations collected in the field along with those collected via remotely using imagery from phenocams, unmanned aerial vehicles (UAVs), and satellite sensors along with estimates of carbon flux. We applied the Breaks for Additive Seasonal and Trend (BFAST) time series algorithm to MODIS 250-m NDVI greenness index values to partition the NDVI signal into components representing the long-term trend, seasonal periodicity, and residuals and identified significant shifts in the NDVI signal (i.e., "breaks"). Previous work verified breaks representing significant deviations from the BFAST seasonal and trend models using field-estimated plant biomass collected between 2000 and 2014. We subsequently examine estimates of fractional cover by functional group derived from UAV images acquired 2010 through 2015. At a mixed grassland site, the BFAST algorithm detected four breaks in the trend model denoting significant increases in NDVI in May 2004, July 2006, and March 2010 and a significant decrease in May 2012. The 2004 and 2006 breaks corresponded to herbaceous vegetation responses to rainfall following prolonged periods of drought. The 2012 decrease in NDVI corresponded to the marked reduction of herbaceous biomass following an exceptionally dry period in late 2010-2011. Seasonal breaks representing changes in the timing and magnitude of NDVI identified in July 2006 and September 2008 coincide with rapid increases in production of annual species in

ENGLISH ABSTRACT: This paper discusses the results obtained from studies on different Rapid Tooling process chains in order to improve the design and manufacture of foundry equipment that is used for sand casting of prototypes in final material. These prototypes are intended for functional and pre-production tests of vehicles. The Three Dimensional Printing process is used as core technology. Subsequently, while considering aspects such as time, cost, quality (accuracy and surface roughness, and tool life, a framework is presented for the evaluation and selection of the most suitable process chain in accordance with specific requirements. This research builds on an in-depth characterisation of the accuracy and repeatability of a 3D printing process.

Severe combined immunodeficiency (SCID), a syndrome of profoundly impaired cellular and humoral immune function, is caused by various autosomal gene defects, including adenosine deaminase (ADA) deficiency, as well as mutations in the X-linked IL2RG gene encoding the gamma chain of the lymphocyte receptor for IL-2. Mutational analysis of IL2RG was performed using genomic DNA from males with SCID referred from genetics and immunology centers. Single strand conformation polymorphisms (SSCP) were sought by PCR amplification of each of the 8 IL2RG exons using labelled flanking primers. Sequence of exons with aberrant SSCP detected a majority of unique deleterious IL2RG mutations in 30 unrelated SCID patients. However, multiple mutations were seen at CpG dinucleotides, known to be C{yields}T transversion sites. cDNA 690-691 in exon 5 was mutated in 4 patients, 1 patient with each of the C{sub 690}{yields}T causing an Arg{yields}Cys substitution, and 1 with G{sub 691}{yields}A causing Arg{yields}His. Two other patients had SCID caused by a single mutation in IL2RG exon 7. This C{sub 879}{yields}T, also in a CpG, changed an Arg to STOP, resulting in loss of the SH2-related intracellular domain. In addition to our patients, 1 patient with each of the C{sub 690} and the C{sub 879} mutations have been reported by others, giving an overall incidence of 20% from our lab and 21% from all reported IL2RG SCID mutations. While ADA defects account for approximately 15% of SCID, a striking male SCID predominance suggest up to 70% of the cases are X-linked, due to IL2RG mutation. Thus, screening for mutations at the 2 CpG hot spots we have found in IL2RG can identify the genotype of as many SCID cases as are found by ADA testing.

Full Text Available The impact of kHz range harmonics on the power losses, thermal stress, and lifetime reduction of the dc-link capacitors in pulse-width modulation (PWM converters was investigated. Expressions to evaluate the mean time to failure, survival probability, and unavailability of aging failure for dc-link capacitors are presented. The dc-link capacitors failures due to accelerated insulation aging were modeled using Weibull and normal distribution. A case study with the Siemens SINAMICS S120 frequency converter for driving of rolling mill leveler shows that the failures of motor modules due to breakdown of electrolytic dc-link capacitors registered for the time frame from May 2012 to October 2012 can be caused by the increased ambient temperature and additional heating due to high-frequency components of the ripple current. As a possible solution to improve reliability of motor modules, the four AVX FFVE4I0227K film capacitors instead of nine EPCOS B43564 electrolytic capacitors in dc-link were recommended.

Patterns of functional diversity reflect the inter- and intraspecific variability of plant traits and are linked to other aspects of biodiversity, environmental factors and ecosystem function. To study the patterns at plot and stand level, spatially continuous trait measurements are required. Remote sensing methods based on airborne observations can offer such continuous high-resolution measurements, resolving individual trees of a forest at a regional extent. The study was performed at the Laegern forest, a temperate mixed forest dominated by deciduous and coniferous trees (Fagus sylvatica, Picea abies; 47°28'42.0" N, 8°21'51.8" E, 682 m asl; Switzerland). Canopy height, plant area index and foliage height diversity were derived from full-waveform airborne laser scanning data. These structural traits were used to calculate functional richness, functional evenness and functional divergence at a range of scales. A Bayesian multiresolution scale analysis was used to infer the scales at which functional diversity patterns occur. The radiative regime of the forest was simulated using the 3D radiative transfer model DART. Using a voxel-based forest reconstruction allowed us to derive top of canopy, bottom of canopy and absorbed photosynthetically active radiation. The results of this study will provide new insights on linking forest canopy structure to the radiative regime of the forest. Light availability is a critical factor determining plant growth and competition. Within canopy light scattering is mainly driven by the arrangement of leaves and their leaf optical properties. Therefore, we expect a link between the structural complexity of the forest as encompassed by functional diversity and the light availability within and below the canopy. Ultimately, this information can be used in dynamic ecosystem models such as ED2, allowing us to predict the influence of functional diversity and radiative properties on ecosystem functioning under current conditions and

Full Text Available Abstract Background Intimin is an important virulence factor involved in the pathogenesis of enteropathogenic Escherichia coli (EPEC and enterohemorrhagic Escherichia coli (EHEC. Both pathogens are still important causes of diarrhea in children and adults in many developing and industrialized countries. Considering the fact that antibodies are important tools in the detection of various pathogens, an anti-intimin IgG2b monoclonal antibody was previously raised in immunized mice with the conserved sequence of the intimin molecule (int388-667. In immunoblotting assays, this monoclonal antibody showed excellent specificity. Despite good performance, the monoclonal antibody failed to detect some EPEC and EHEC isolates harboring variant amino acids within the 338-667 regions of intimin molecules. Consequently, motivated by its use for diagnosis purposes, in this study we aimed to the cloning and expression of the single-chain variable fragment from this monoclonal antibody (scFv. Findings Anti-intimin hybridoma mRNA was extracted and reversely transcripted to cDNA, and the light and heavy chains of the variable fragment of the antibody were amplified using commercial primers. The amplified chains were cloned into pGEM-T Easy vector. Specific primers were designed and used in an amplification and chain linkage strategy, obtaining the scFv, which in turn was cloned into pAE vector. E. coli BL21(DE3pLys strain was transformed with pAE scFv-intimin plasmid and subjected to induction of protein expression. Anti-intimin scFv, expressed as inclusion bodies (insoluble fraction, was denatured, purified and submitted to refolding. The protein yield was 1 mg protein per 100 mL of bacterial culture. To test the functionality of the scFv, ELISA and immunofluorescence assays were performed, showing that 275 ng of scFv reacted with 2 mg of purified intimin, resulting in an absorbance of 0.75 at 492 nm. The immunofluorescence assay showed a strong reactivity with

Full Text Available Intercellular adhesion molecule-1 (ICAM-1 is an important factor in the progression of inflammatory responses in vivo. To develop a new anti-inflammatory drug to block the biological activity of ICAM-1, we produced a monoclonal antibody (Ka=4.19×10−8 M against human ICAM-1. The anti-ICAM-1 single-chain variable antibody fragment (scFv was expressed at a high level as inclusion bodies in Escherichia coli. We refolded the scFv (Ka=2.35×10−7 M by ion-exchange chromatography, dialysis, and dilution. The results showed that column chromatography refolding by high-performance Q Sepharose had remarkable advantages over conventional dilution and dialysis methods. Furthermore, the anti-ICAM-1 scFv yield of about 60 mg/L was higher with this method. The purity of the final product was greater than 90%, as shown by denaturing gel electrophoresis. Enzyme-linked immunosorbent assay, cell culture, and animal experiments were used to assess the immunological properties and biological activities of the renatured scFv.

CD8 glycoproteins are expressed as either alphaalpha homodimers or alphabeta heterodimers on the surface of T cells. CD8alphabeta is a more efficient coreceptor than the CD8alphaalpha for peptide Ag recognition by TCR. Each CD8 subunit is composed of four structural domains, namely, Ig-like domain, stalk region, transmembrane region, and cytoplasmic domain. In an attempt to understand why CD8alphabeta is a better coreceptor than CD8alphaalpha, we engineered, expressed, and functionally tested a chimeric CD8alpha protein whose stalk region is replaced with that of CD8beta. We found that the beta stalk region enhances the coreceptor function of chimeric CD8alphaalpha to a level similar to that of CD8alphabeta. Surprisingly, the beta stalk region also restored functional activity to an inactive CD8alpha variant, carrying an Ala mutation at Arg(8) (R8A), to a level similar to that of wild-type CD8alphabeta. Using the R8A variant of CD8alpha, a panel of anti-CD8alpha Abs, and three MHC class I (MHCI) variants differing in key residues known to be involved in CD8alpha interaction, we show that the introduction of the CD8beta stalk leads to a different topology of the CD8alpha-MHCI complex without altering the overall structure of the Ig-like domain of CD8alpha or causing the MHCI to employ different residues to interact with the CD8alpha Ig domain. Our results show that the stalk region of CD8beta is capable of fine-tuning the coreceptor function of CD8 proteins as a coreceptor, possibly due to its distinct protein structure, smaller physical size and the unique glycan adducts associated with this region.

present a novel low-parameter approach to describe glycosylation using flux-balance and Markov chain modeling. The model recapitulates the biological complexity of glycosylation, but does not require user-provided kinetic information. We use this method to predict and experimentally validate glycoprofiles...

The effects of ..cap alpha..-D-mannopyranosylmethyl-p-nitrophenyltriazene (..cap alpha..-ManMNT) on the degradation and processing of oligosaccharide chains on ..cap alpha../sub 1/-acid glycoprotein (AGP) were studied. Addition of the triazene to a perfused liver blocked the complete degradation of endocytosed N-acetyl (/sup 14/C)glucosamine-labeled asialo-AGP and caused the accumulation of Man/sub 2/GlcNAc/sub 1/ fragments in the lysosome-enriched fraction of the liver homogenate. This compound also reduced the reincorporation of lysosomally-derived (/sup 14/C)GlcNAc into newly secreted glycoproteins. Cultured hepatocytes treated with the inhibitor synthesized and secreted fully-glycosylated AGP. However, the N-linked oligosaccharide chains on AGP secreted by the ..cap alpha..-ManMNT-treated hepatocytes remained sensitive to digestion with endoglycosidase H, were resistant to neuraminidase, and consisted of Man/sub 9-7/GlcNAc/sub 2/ structures as analyzed by high resolution Bio-Gel P-4 chromatography. As measured by their resistance to cleavage by endoglycosidase H, the normal processing of all six carbohydrate chains on AGP to the complex form did not completely resume until nearly 24 h after triazene treatment. Since ManMNT is likely to irreversibly inactivate ..cap alpha..-D-mannosidases, the return of AGP to secretory forms with complex chains after 24 h probably resulted from synthesis of new processing enzymes.

An optimized version of the Nested Markov Chain Monte Carlo sampling method is applied to the calculation of the Hugoniot for liquid nitrogen. The 'full' system of interest is calculated using density functional theory (DFT) with a 6-31 G* basis set for the configurational energies. The 'reference' system is given by a model potential fit to the anisotropic pair interaction of two nitrogen molecules from DFT calculations. The EOS is sampled in the isobaric-isothermal (NPT) ensemble with a trial move constructed from many Monte Carlo steps in the reference system. The trial move is then accepted with a probability chosen to give the full system distribution. The P's and T's of the reference and full systems are chosen separately to optimize the computational time required to produce the full system EOS. The method is numerically very efficient and predicts a Hugoniot in excellent agreement with experimental data.

FADD protein is a critical mediator of signal transduction pathways activated by several members of the TNF-receptor gene superfamily. Recently, an induced proximity model has been proposed to interpret FADD-mediated signaling events. According to this model, FADD facilitates signaling by inducing clusters of effector molecules in proximity of the activated receptor complex. An important corollary of the induced-proximity model is that FADD protein should not form oligomers in the absence of receptor stimulation. Here we show that, in the absence of death receptor stimulation, FADD is found associated to the alpha chain of the nascent polypeptide-associated complex (NAC). Exposure to TNF results in disruption of FADD/NAC complex. Expression of NAC regulates formation of FADD oligomers and modulates FADD-mediated signaling. Thus, our observation indicates that NAC may serve as an intracellular regulator of FADD function.

We derive the dominant contribution to the large-distance decay laws of correlation functions towards their asymptotic limits for a spin chain model that exhibits both Haldane and Neel phases in its ground-state phase diagram. The analytic results are obtained by means of an approximate mapping between a spin-1 anisotropic Hamiltonian onto a fermionic model of noninteracting Bogoliubov quasiparticles related in turn (via Jordan-Wigner transformation) to the XY spin-1/2 chain in a transverse field. This approach allows us to express the spin-1 string operators in terms of fermionic operators so that the dominant contribution to the string correlators at large distances can be computed using the technique of Toeplitz determinants. As expected, we find long-range string order both in the longitudinal and in the transverse channel in the Haldane phase, while in the Neel phase only the longitudinal order survives. In this way, the long-range string order can be explicitly related to the components of the magnetization of the XY model. Moreover, apart from the critical line, where the decay is algebraic, we find that in the gapped phases the decay is governed by an exponential tail multiplied by power-law factors. As regards the usual two points correlation functions, we show that the longitudinal one behaves in a 'dual' fashion with respect to the transverse string correlator, namely both the asymptotic values and the decay laws exchange when the transition line is crossed. For the transverse spin-spin correlator, we always find a finite characteristic length which is an unexpected feature at the critical point. The results of this analysis prove some conjectures put forward in the past. We also comment briefly on the entanglement features of the original system versus those of the effective model. The goodness of the approximation and the analytical predictions are checked versus density-matrix renormalization group calculations.

@@ An extended test-particle method is used to predict the inter- and intramolecular correlation functions of freely jointed hard-sphere-Yukawa-chain fluids by calculating the segmental density distributions around a fixed seg ment. The underlying density functional theory for chain fluids is based on a modified fundamental measure theory for the hard-sphere repulsive and a mean-field approximation for attraction between different segments.The calculated intra- and inter-molecular distribution functions agree well with the results from Monte Carlo simulations, better than those from alternative approaches.

This study investigated the prospective links between sleep in infancy and preschoolers' cognitive performance. Mothers of 65 infants completed a sleep diary when infants were aged 1 year, and children completed two subscales of the Wechsler Preschool and Primary Scale of Intelligence at 4 years, indexing general cognitive ability and complex…

The placenta is an essential organ formed during pregnancy that mainly transfers nutrients from the mother to the fetus. Nutrients taken up by the placenta are required for its own growth and development and to optimize fetal growth. Hence, placental function is an important determinant of pregnancy outcome. Among various nutrients, fatty acids, especially long-chain polyunsaturated fatty acids (LCPUFAs), including omega 3 and omega 6 fatty acids, are essential for placental development from the time of implantation. Studies have associated these LCPUFAs with placental development through their roles in regulating oxidative stress, angiogenesis, and inflammation, which may in turn influence their transfer to the fetus. The placenta has a heterogeneous morphology with variable regional vasculature, oxidative stress, and LCPUFA levels in healthy pregnancies depending upon the location within the placenta. However, these regional structural and functional parameters are found to be disturbed in pathological conditions, such as preeclampsia (PE), thereby affecting pregnancy outcome. Hence, the alterations in LCPUFA metabolism and transport in different regions of the PE placenta as compared with normal placenta could potentially be contributing to the pathological features of PE. The regional variations in development and function of the placenta and its possible association with placental LCPUFA metabolism and transport in normal and PE pregnancies are discussed in this review. WIREs Dev Biol 2016, 5:582-597. doi: 10.1002/wdev.238 For further resources related to this article, please visit the WIREs website.

PUF family translational repressors are conserved developmental regulators, but the molecular function provided by the regions flanking the PUF RNA-binding domain is unknown. In C. elegans, the PUF proteins FBF-1 and FBF-2 support germline progenitor maintenance by repressing production of meiotic proteins and use distinct mechanisms to repress their target mRNAs. We identify dynein light chain DLC-1 as an important regulator of FBF-2 function. DLC-1 directly binds to FBF-2 outside of the RNA-binding domain and promotes FBF-2 localization and function. By contrast, DLC-1 does not interact with FBF-1 and does not contribute to FBF-1 activity. Surprisingly, we find that the contribution of DLC-1 to FBF-2 activity is independent of the dynein motor. Our findings suggest that PUF protein localization and activity are mediated by sequences flanking the RNA-binding domain that bind specific molecular partners. Furthermore, these results identify a new role for DLC-1 in post-transcriptional regulation of gene expression.

Full Text Available This paper presents a possible alternative to traditional cellulose nanofibers functionalization, by treatment of the material at low temperatures (25–35°C with electron-beam irradiated 1-hexyl-3-methylimidazolium chloride ionic liquid. The treatment promotes decreasing the crystallinity of the cellulose with up to 45% and possible imidazolium moieties grafting to cellulose, as demonstrated from FTIR, XRD, and elemental analysis. The grafting determines water vapors uptake values with 50–70% lower and water vapors uptake rate with 50% lower than those of reference cellulose nanofibers. The grafting determined also improved adhesion of the cellulose nanofibers to HDPE, thus contributing to the obtaining of polymer matrix composites with improved properties.

A quantum-mechanical (QM) method rooted on density functional theory (DFT) has been employed to determine conformations of the methane-thiosulfonate spin label (MTSL) attached to a fragment extracted from the activation loop of Aurora-A kinase. The features of the calculated energy surface revealed low energy barriers between isoenergetic minima and the system could be described in a population of 76 rotamers that can be also considered for other systems since it was found that the X3, X4 and X5 do not depend on the previous two dihedral angles. Conformational states obtained were seen to comparable to those obtained in the {\\alpha}-helix systems studied previously, indicating that the protein backbone does not affect the torsional profiles significantly and suggesting the possibility to use determined conformations for other protein systems for further modelling studies.

A large number of genes are necessary for the biosynthesis and activity of the enzyme nitrogenase to carry out the process of biological nitrogen fixation (BNF), which requires large amounts of ATP and reducing power. The multiplicity of the genes involved, the oxygen sensitivity of nitrogenase, plus the demand for energy and reducing power, are thought to be major obstacles to engineering BNF into cereal crops. Genes required for nitrogen fixation can be considered as three functional modules encoding electron-transport components (ETCs), proteins required for metal cluster biosynthesis, and the "core" nitrogenase apoenzyme, respectively. Among these modules, the ETC is important for the supply of reducing power. In this work, we have used Escherichia coli as a chassis to study the compatibility between molybdenum and the iron-only nitrogenases with ETC modules from target plant organelles, including chloroplasts, root plastids, and mitochondria. We have replaced an ETC module present in diazotrophic bacteria with genes encoding ferredoxin-NADPH oxidoreductases (FNRs) and their cognate ferredoxin counterparts from plant organelles. We observe that the FNR-ferredoxin module from chloroplasts and root plastids can support the activities of both types of nitrogenase. In contrast, an analogous ETC module from mitochondria could not function in electron transfer to nitrogenase. However, this incompatibility could be overcome with hybrid modules comprising mitochondrial NADPH-dependent adrenodoxin oxidoreductase and the Anabaena ferredoxins FdxH or FdxB. We pinpoint endogenous ETCs from plant organelles as power supplies to support nitrogenase for future engineering of diazotrophy in cereal crops.

. However, to be a practical tool in the surveillance of drug resistance, simpler methods for high-throughput haplotyping are warranted. Here we describe a quick and simple technique that detects dhfr, dhps, and Pfcrt SNPs using polymerase chain reaction (PCR)- and enzyme-linked immunosorbent assay (ELISA...... the SNPs of dhfr, dhps, and Pfcrt with high specificity. The SSOP-ELISA compared well with a standard PCR-restriction fragment length polymorphism procedure, and gave identical positive results in more than 90% of the P. falciparum slide-positive samples tested. The SSOP-ELISA of all dhfr, dhps, or Pfcrt...

[BMIm]4[AgMo10Cl35] is prepared by reaction of MoCl5 and elemental silver in the ionic liquid [BMIm][AlCl4] ([BMIm(+)]: 1-butyl-4-methylimidazolium). Surprisingly, elemental silver is oxidized under these conditions. The title compound contains a new wheel-shaped [Mo10Cl35](5-) chlorido molybdenum(iii) species with five pairs of Mo-Mo bonds. The Mo-Mo distances are found to be 263 pm on average. The [Mo10Cl35](5-) wheels exhibit a maximum opening of 558 pm in diameter. They are interlinked via Ag(+) to form infinite [AgMo10Cl35](4-) chains. The title compound is characterized by single crystal structure analysis, EDX, FT-IR and UV-Vis spectroscopy. The wheel-type structure and Ag(+) linkage to infinite chains are a new aspect of halogenido metalates and low-valence molybdenum compounds.

Gaussian noise is one of the dominant noises, which degrades the quality of acquired Computed Tomography (CT) image data. It creates difficulties in pathological identification or diagnosis of any disease. Gaussian noise elimination is desirable to improve the clarity of a CT image for clinical, diagnostic, and postprocessing applications. This paper proposes an evolutionary nonlinear adaptive filter approach, using Cat Swarm FunctionalLink Artificial Neural Network (CS-FLANN) to remove the ...

.... Several functional traits have been shown to correlate with growth and mortality rates in trees, but less is known about how the relationships between functional traits and demographic rates change with tree size...

Impact of dispersion quality of NH{sub 2}-MWCNTs (13–18 nm in diameter with a length between 1 and 12 µm, >99 % purity) in the amplification efficiency of a random DNA oligonucleotide library (96 bp) was investigated. Amplification yield in the presence of non-filtered NH{sub 2}-MWCNT dispersion, filtered NH{sub 2}-MWCNT dispersion and surface-attached NH{sub 2}-MWCNTs was explored, and physical interactions between NH{sub 2}-MWCNTs and major PCR reagents including DNA template, wild type Taq DNA polymerase enzyme and primers were determined using high resolution polyacrylamide gel electrophoresis, dynamic light scattering, UV–Vis-NIR spectroscopy and scanning electron microscopy techniques. The results revealed that presence of NH{sub 2}-MWCNT dispersion which was sonicated, centrifuged and filtered, enhanced the total PCR efficiency up to 70 % while the presence of NH{sub 2}-MWCNT only centrifuged after sonication, inhibited the reaction significantly at similar concentrations. Furthermore, the NH{sub 2}-MWCNTs coupled covalently onto magnetic microspheres, contributed for the specificity enhancement whilst decreasing the amplification efficiency by 30 % at the maximum concentration, which suggests a removable enhancement system for sensitive applications. On the other hand, the relative hydrodynamic size distribution measurements displayed a clear difference between the filtered NH{sub 2} and non-filtered NH{sub 2}-MWCNT water dispersions, which justifies the inhibition of the amplification by the non-filtered NH{sub 2}-MWCNTs containing big agglomerates and bundles. Finally, we demonstrated that major PCR components adsorb onto the NH{sub 2}-MWCNTs with diverse affinities, and maintain their functions after adsorption, which provides a good framework to further develop tunable NH{sub 2}-MWCNT-carriers to be utilized in various nanobiotechnology and material science applications.

The life support systems (LSS) for long-term missions are to use cycling-recycling systems, including biological recycling. Simple ecosystems include 3 links: producers (plants), consumers (man, animals) and reducers (microorganisms). Microorganisms are substantial component of every link of LSS. Higher plants are the traditional regenerator of air and producer of food. They should be used in many successive generations of their reproduction in LSS. Controlled microbiocenoses can increase productivity of producer's link and protect plants from infections. The goal of this work was development of methodological bases of formation of stable, controlled microbiocenoses, intended for increase of productivity of plants and for obtaining ecologically pure production of plants. Main results of our investigations: 1. Experimental microbiocenoses, has been produced in view of the developed methodology on the basis of natural association of microorganisms by long cultivation on specially developed medium. Dominating groups are bacteria of genera: Lactobacillus, Streptococcus, Leuconostoc, Bifidobacterium, Rhodopseudomonas and yeast of genera: Kluyveromyces, Saccharomyces, Torulopsis. 2. Optimal parameters of microbiocenosis cultivation (t, pH, light exposure, biogenic elements concentrations) were experimentally established. Conditions of cultivation on which domination of different groups of microbiocenosis have been found. 3. It was shown, that processing of seeds of wheat, oats, bulbs and plants Allium cepa L. (an onions) with microbial association raised energy of germination of seeds and bulbs and promoted the increase (on 20-30 %) of growth green biomass and root system of plants in comparison with the control. This work is supported by grant, Yenissey , 07-04-96806

plasma AA and DHA levels and both MDI and PDI scores. From the course of this study we concluded that malnourished infants had impaired neurodevelopmental functions that could be related to the poor status of plasma LC-PUF. Thus, we recommend early intervention including nutritional rehabilitation and LC-PUFA supplementation as well as stimulation program, so as to have a better effect on future cognitive abilities of these infants.

Trophic links of soil animals are extensively diverse but also flexible. Moreover, feeding activity of large soil saprotrophs often cascades into a range of ecosystem-level consequences via the ecological engineering. Better knowledge on the main sources of energy utilized by soil animals is needed for understanding functional structure of soil animal communities and their participation in the global carbon cycling. Using published and original data, we consider the relative importance of dead organic matter and saprotrophic microorganisms as a basal energy source in the detritus-based food chains, the feeding of endogeic macrofauna on the stabilized soil organic matter, and the role of recent photosynthate in the energy budget of soil communities. Soil food webs are spatially and functionally compartmentalized, though the separation of food chains into bacteria- and fungi-based channels seems to be an over-simplification. The regulation of the litter decomposition rates via top-down trophic interactions across more than one trophic level is only partly supported by experimental data, but mobile litter-dwelling predators play a crucial role in integrating local food webs within and across neighboring ecosystems.

Full Text Available Soil microorganisms are key players in biogeochemical cycles. Yet, there is no consistent view on the significance of microbial biodiversity for soil ecosystem functioning. According to the insurance hypothesis, declines in ecosystem functioning due to reduced biodiversity are more likely to occur under fluctuating, extreme or rapidly changing environmental conditions. Here, we compare the functional operating range, a new concept defined as the complete range of environmental conditions under which soil microbial communities are able to maintain their functions, between four naturally assembled soil communities from a long-term fertilization experiment. A functional trait approach was adopted with denitrifiers involved in nitrogen cycling as our model soil community. Using short-term temperature and salt gradients, we show that the functional operating range was broader and process rates were higher when the soil community was phylogenetically more diverse. However, key bacterial genotypes played an important role for maintaining denitrification as an ecosystem functioning under certain conditions.

This guide provides a set of concepts and analytical tools for finding ways to better link small-scale producers to the modern markets associated with today’s largescale supermarket retail and wholesale operations. It is has been developed through iterative testing with partners in several organisat

Full Text Available We identified and characterized the primary structure of the Korean oily bitterling Acheilognathus koreensis fast skeletal myosin light chain 2 (Akmlc2f, gene. Encoded by seven exons spanning 3955 bp, the deduced 168-amino acid AkMLC2f polypeptide contained an EF-hand calcium-binding motif and showed strong homology (80%–98% with the MLC2 proteins of Ictalurus punctatus and other species, including mammals. Akmlc2f mRNA was highly enriched in skeletal muscles, and was detectable in other tissues. The upstream regions of Akmlc2f included a TATA box, one copy of a putative MEF-2 binding site and several putative C/EBPβ binding sites. The functional activity of the promoter region of Akmlc2f was examined using luciferase and red fluorescent protein reporters. The Akmlc2f promoter-driven reporter expressions were detected and increased by the C/EBPβ transcription factor in HEK293T cells. The activity of the promoter of Akmlc2f was also confirmed in the developing zebrafish embryo. Although the detailed mechanism underlying the expression of Akmlc2f remains unknown, these results suggest the muscle-specific expression of Akmlc2f transcript and the functional activation of Akmlc2f promoter by C/EBPβ.

Mixed-effect Markov chain models have been recently proposed to characterize the time course of transition probabilities between sleep stages in insomniac patients. The most recent one, based on multinomial logistic functions, was used as a base to develop a final model combining the strengths of the existing ones. This final model was validated on placebo data applying also new diagnostic methods and then used for the inclusion of potential age, gender, and BMI effects. Internal validation was performed through simplified posterior predictive check (sPPC), visual predictive check (VPC) for categorical data, and new visual methods based on stochastic simulation and estimation and called visual estimation check (VEC). External validation mainly relied on the evaluation of the objective function value and sPPC. Covariate effects were identified through stepwise covariate modeling within NONMEM VI. New model features were introduced in the model, providing significant sPPC improvements. Outcomes from VPC, VEC, and external validation were generally very good. Age, gender, and BMI were found to be statistically significant covariates, but their inclusion did not improve substantially the model's predictive performance. In summary, an improved model for sleep internal architecture has been developed and suitably validated in insomniac patients treated with placebo. Thereafter, covariate effects have been included into the final model.

Full Text Available Regarding the application of vegetable oil based fuels in diesel engines, it is necessary to fully examine and understand the processes which take place in fuel delivery systems, namely, the processes of injection, mixture formation and combustion as well as emission characteristics. The paper provides an analysis of fuel flow in high pressure tubes of the fuel injection system, with the aim of determining function K as a link between fuel flow velocity and fuel pressure, and observing the influence of certain physical characteristics of the fuel upon the given function. The analysis presents the speed of sound and density, as fuel characteristics which affect the K function. The paper determines the speed of sound, density and bulk modulus for four fuels (pure rapeseed oil RO, biodiesel B100, a mixture of biodiesel and diesel B50, and diesel D, and forms appropriate K functions for each fuel in the pressure range from the atmospheric one to 1600 bar.

Polycystic ovary syndrome (PCOS) is the most common endocrinopathy associated with infertility and metabolic disorder in women of reproductive age. Dysfunction of adipose tissue has been implicated in the pathophysiology of PCOS. Increasing evidence shows that the dysregulated expression of adipokines, the secreted products of adipose tissue, plays an important role in the pathology of PCOS. Here, we review the role of several identified adipokines that may act as a link between obesity and PCOS. PCOS also reciprocally influences the profile of adipokines. Insight into the underlying mechanisms will help better understand the pathology of PCOS and identify new therapeutic targets of this syndrome.

KC-TZ118型链轨节数控钻镗组合机床,是校企合作共同研发的高效率、高精度、高性能自动钻镗组合机床,专门用于挖掘机左右链轨节镗孔、钻孔的加工.主要介绍KC-TZ118型链轨节数控钻镗组合机床的方案确定、机床结构特点、机床参数的配置、数控系统的配置及调试方法等,并详细分析机床设计中的关键技术.%KC-TZ118 CNC drilling and boring modular machine for chainlink, a kind of high efficient, high precise and high performance automatic drilling and boring modular machine developed by enterprise and school, is especially used for boring hole and drilling hole processing of the left and right chainlink of the excavator.The program determination, structural characteristics of the machine, and parameter configuration of the machine, the numerical control system configuration and debugging methods of KC-TZ118CNC drilling and boring modular machine were introduced, in addition, the key techniques of design for machine were analyzed in detail.

evidence of the employee-customer-profit chain. As it is possible to estimate the links, we have demonstrated their effect on company profitability. The research findings provide a better understanding of the service-profit chain and may help practitioners in improving company financial performance.......This paper examines the links between employee attitudes, customer loyalty and company profitability. From a conceptual point of view, this employee-customer-profit chain, also known as the service-profit chain, is well founded and generally accepted. But for many companies, it seems difficult...... to demonstrate such links, and several issues must be addressed to uncover the links. To investigate these links empirically, a hotel chain provided data matching employee and customer measures with measures of profitability. We have successfully employed a modeling approach, and the paper reports empirical...

Matrix-assisted laser desorption ionization (MALDI) time-of-flight (TOF) mass spectrometry (MS) is applied to examine the products arising upon the preparation of chain-end functional polymers via living anionic polymerization techniques. Both post-polymerization functionalizations as well as the use of functionalized initiators are investigated. MALDI-TOF MS is shown to be a sensitive probe for the qualitative analysis of the major and minor oligomers from novel functionalization reactions whose mechanisms are not yet well established. The method is particularly valuable for the identification of the end groups of the minor, and often unexpected, distributions that may be undetectable by other analytical means. Complete characterization of all oligomers generated during functionalization reactions provides an essential tool to the synthetic chemist for understanding the corresponding mechanisms. This insight is necessary for selecting alternative routes or making modifications to the reaction conditions. It is demonstrated that MALDI-TOF MS can convey quantitative information about the yields of the chain-end groups introduced during functionalization. From the cases presented it is evident that post-polymerization reactions allow for better control of chain-end functionality and molecular weight than functionalization with the limited number of currently available protected functionalized initiators.

This paper addresses one major cause for large uncertainties in human reliability analysis (HRA) results, that is, an absence of detailed function, task, timeline, link and human vulnerability analyses. All too often this crucial step in the HRA process is done in a cursory fashion using word of mouth or written procedures which themselves may incompletely or inaccurately represent the human action sequences and human error vulnerabilities being analyzed. The paper examines the potential contributions these detailed analyses can make in achieving quantitative and qualitative HRA results which are: (1) creditable, that is, minimize uncertainty, (2) auditable, that is, systematically linking quantitative results and qualitative information from which the results are derived, (3) capable of supporting root cause analyses on human reliability factors determined to be major contributors to risk, and (4) capable of repeated measures and being combined with similar results from other analyses to examine HRA issues transcending individual systems and facilities. Based on experience analyzing test and commercial nuclear reactors, and medical applications of nuclear technology, an iterative process is suggested for doing detailed function, task, timeline, link and human vulnerability analyses using documentation reviews, open-ended and structured interviews, direct observations, and group techniques. Finally, the paper concludes that detailed analyses done in this manner by knowledgeable human factors practitioners, can contribute significantly to the credibility, auditability, causal factor analysis, and combining goals of the HRA.

Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disease with dysfunctional α-motor neurons in the anterior horn of the spinal cord. SMA is caused by loss (∼95% of SMA cases) or mutation (∼5% of SMA cases) of the survival motor neuron 1 gene SMN1. As the product of SMN1, SMN is a component of the SMN complex, and is also involved in the biosynthesis of the small nuclear ribonucleoproteins (snRNPs), which play critical roles in pre-mRNA splicing in the pathogenesis of SMA. To investigate how SMA-linked mutations of SMN1 lead to structural/functional deficiency of SMN, a set of computational analysis of SMN-related structures were conducted and are described in this article. Of extraordinary interest, the structural analysis highlights three SMN residues (Asp44, Glu134 and Gln136) with SMA-linked missense mutations, which cause disruptions of electrostatic interactions for Asp44, Glu134 and Gln136, and result in three functionally deficient SMA-linked SMN mutants, Asp44Val, Glu134Lys and Gln136Glu. From the computational analysis, it is also possible that SMN's Lys45 and Asp36 act as two electrostatic clips at the SMN-Gemin2 complex structure interface.

of twins from the Longitudinal Study of Aging Danish Twins. Cognitive function was measured using forward and backward digit span, immediate and delayed memory, and fluency tasks. Physical function was measured using self-report of ability to carry out physical activities including walking, running...

Although depression and immune changes in elderly subjects constitute a considerable health risk, mechanisms underlying the association between depression and immune function are unclear. The question of whether personality and social support can explain the variation in immune function during depre

Single-chain polymeric nanoparticles (SCPNs) are intriguing systems for multiple applications. In order to arrive at a controlled, but random, positioning of the different side groups to the polymer backbone, alternative synthetic routes have to be developed. Here, a general postpolymerization modification strategy of poly(pentafluorophenyl acrylate) (pPFPA) is presented as a versatile method to rapidly access functional SCPNs. We first show that the sequential addition of a benzene-1,3,5-tricarboxamide-based amine, acting as the supramolecular recognition motif, and water-soluble polyetheramine (Jeffamine) to pPFPA affords random copolymers that fold in water into SCPNs. The scope of the modular platform is illustrated by preparing two types of functional SCPNs. First, we prepared SCPNs designed for bio-orthogonal catalysis by attaching pendant mono(benzimidazoylmethyl)-bis(pyridylmethyl) (Bimpy), phenanthroline (Phen), or 2,2'-bipyridine (BiPy), ligands capable of binding either Cu(I) or Pd(II). The Bimpy- and Phen-containing SCPNs ligated to Cu(I) significantly accelerate azide-alkyne cycloaddition reactions while Bipy-containing SCPNs ligated to Pd(II) efficiently catalyze depropargylation reactions. In all cases, reactions proceeded efficiently in phosphate buffer at a physiological pH and at low substrate concentrations. Next, the potential of SCPNs for photodynamic therapy was evaluated. Introducing porphyrins in SCPNs leads to novel photosensitizers that can produce singlet oxygen ((1)O2) upon photoirradiation. Additionally, by attaching both porphyrins and prodrug models, attached via (1)O2-cleavable amino-acrylate linker, to the SCPNs, we show that irradiation of the SCPNs results in a cascade reaction of (1)O2 generation followed by cleavage of the amino-acrylate linkers, releasing the drug model. The modular synthesis strategy reported here provides rapid and controlled access to SCPNs with tunable amounts of active units that fulfill different

N-glycosylation of proteins is one of the most prevalent posttranslational modifications in nature. Accordingly, a pathway with shared commonalities is found in all three domains of life. While excellent model systems have been developed for studying N-glycosylation in both Eukarya and Bacteria, an understanding of this process in Archaea was hampered until recently by a lack of effective molecular tools. However, within the last decade, impressive advances in the study of the archaeal version of this important pathway have been made for halophiles, methanogens, and thermoacidophiles, combining glycan structural information obtained by mass spectrometry with bioinformatic, genetic, biochemical, and enzymatic data. These studies reveal both features shared with the eukaryal and bacterial domains and novel archaeon-specific aspects. Unique features of N-glycosylation in Archaea include the presence of unusual dolichol lipid carriers, the use of a variety of linking sugars that connect the glycan to proteins, the presence of novel sugars as glycan constituents, the presence of two very different N-linked glycans attached to the same protein, and the ability to vary the N-glycan composition under different growth conditions. These advances are the focus of this review, with an emphasis on N-glycosylation pathways in Haloferax, Methanococcus, and Sulfolobus.

Psychosis is linked to dysregulation of the neuromodulator dopamine and antipsychotic drugs (APDs) work by blocking dopamine receptors. Dopamine-modulated disruption of latent inhibition (LI) and conditioned avoidance response (CAR) have served as standard animal models of psychosis and antipsychotic action, respectively. Meanwhile, the 'temporal difference' algorithm (TD) has emerged as the leading computational model of dopamine neuron firing. In this report TD is extended to include action at the level of dopamine receptors in order to explain a number of behavioral phenomena including the dose-dependent disruption of CAR by APDs, the temporal dissociation of the effects of APDs on receptors vs behavior, the facilitation of LI by APDs, and the disruption of LI by amphetamine. The model also predicts an APD-induced change to the latency profile of CAR--a novel prediction that is verified experimentally. The model's primary contribution is to link dopamine neuron firing, receptor manipulation, and behavior within a common formal framework that may offer insights into clinical observations.

Working memory, the capacity of actively maintaining task-relevant information during a cognitive task, is a heritable trait. Working memory deficits are characteristic for many psychiatric disorders. We performed genome-wide gene set enrichment analyses in multiple independent data sets of young and aged cognitively healthy subjects (n = 2,824) and in a large schizophrenia case-control sample (n = 32,143). The voltage-gated cation channel activity gene set, consisting of genes related to neuronal excitability, was robustly linked to performance in working memory-related tasks across ages and to schizophrenia. Functional brain imaging in 707 healthy participants linked this gene set also to working memory-related activity in the parietal cortex and the cerebellum. Gene set analyses may help to dissect the molecular underpinnings of cognitive dimensions, brain activity, and psychopathology.

Full Text Available BACKGROUND: Genome-wide association studies (gwas are invaluable in revealing the common variants predisposing to complex human diseases. Yet, until now, the large volumes of data generated from such analyses have not been explored extensively enough to identify the molecular and functional framework hosting the susceptibility genes. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the relationships among five neurodegenerative and/or autoimmune complex human diseases (Parkinson's disease--Park, Alzheimer's disease--Alz, multiple sclerosis--MS, rheumatoid arthritis--RA and Type 1 diabetes--T1D by characterising the interactomes linked to their gwas-genes. An initial study on the MS interactome indicated that several genes predisposing to the other autoimmune or neurodegenerative disorders may come into contact with it, suggesting that susceptibility to distinct diseases may converge towards common molecular and biological networks. In order to test this hypothesis, we performed pathway enrichment analyses on each disease interactome independently. Several issues related to immune function and growth factor signalling pathways appeared in all autoimmune diseases, and, surprisingly, in Alzheimer's disease. Furthermore, the paired analyses of disease interactomes revealed significant molecular and functional relatedness among autoimmune diseases, and, unexpectedly, between T1D and Alz. CONCLUSIONS/SIGNIFICANCE: The systems biology approach highlighted several known pathogenic processes, indicating that changes in these functions might be driven or sustained by the framework linked to genetic susceptibility. Moreover, the comparative analyses among the five genetic interactomes revealed unexpected genetic relationships, which await further biological validation. Overall, this study outlines the potential of systems biology to uncover links between genetics and pathogenesis of complex human disorders.

Functional trait analysis is an appealing approach to study differences among biological communities because traits determine species' responses to the environment and their impacts on ecosystem functioning. Despite a rapidly expanding quantitative literature, it remains challenging to conceptualize concurrent changes in multiple trait dimensions ("trait space") and select quantitative functional diversity methods to test hypotheses prior to analysis. To address this need, we present a widely applicable framework for visualizing ecological phenomena in trait space to guide the selection, application, and interpretation of quantitative functional diversity methods. We describe five hypotheses that represent general patterns of responses to disturbance in functional community ecology and then apply a formal decision process to determine appropriate quantitative methods to test ecological hypotheses. As a part of this process, we devise a new statistical approach to test for functional turnover among communities. Our combination of hypotheses and metrics can be applied broadly to address ecological questions across a range of systems and study designs. We illustrate the framework with a case study of disturbance in freshwater communities. This hypothesis-driven approach will increase the rigor and transparency of applied functional trait studies.

Full Text Available Following severe injuries that result in disorders of consciousness, recovery can occur over many months or years post-injury. While post-injury synaptogenesis, axonal sprouting and functional reorganization are known to occur, the network-level processes underlying recovery are poorly understood. Here, we test a network-level functional rerouting hypothesis in recovery of patients with disorders of consciousness following severe brain injury. This hypothesis states that the brain recovers from injury by restoring normal functional connections via alternate structural pathways that circumvent impaired white matter connections. The so-called network diffusion model, which relates an individual's structural and functional connectomes by assuming that functional activation diffuses along structural pathways, is used here to capture this functional rerouting. We jointly examined functional and structural connectomes extracted from MRIs of 12 healthy and 16 brain-injured subjects. Connectome properties were quantified via graph theoretic measures and network diffusion model parameters. While a few graph metrics showed groupwise differences, they did not correlate with patients' level of consciousness as measured by the Coma Recovery Scale — Revised. There was, however, a strong and significant partial Pearson's correlation (accounting for age and years post-injury between level of consciousness and network diffusion model propagation time (r = 0.76, p functional activation spends traversing the structural network. We concluded that functional rerouting via alternate (and less efficient pathways leads to increases in network diffusion model propagation time. Simulations of injury and recovery in healthy connectomes confirmed these results. This work establishes the feasibility for using the network diffusion model to capture network-level mechanisms in recovery of consciousness after severe brain injury.

to assay in vivo regional brain chemistry and function, respectively. Typically, these neuroimaging modalities are implemented independently despite the capacity for integrated data sets to offer unique insight into molecular mechanisms associated with brain function. Through examples from the serotonin...... and dopamine system and its effects on threat- and reward-related brain function, we review evidence for how such a multimodal neuroimaging strategy can be successfully implemented. Furthermore, we discuss how multimodal PET-fMRI can be integrated with techniques such as imaging genetics, pharmacological...

...s. Nitrification occurs when soil microbes convert ammonium to nitrate. Nitrification is known to be regulated by abiotic soil properties, but less is known about how plant communities influence this important ecosystem function. 2...

Temperament is associated with important outcomes in adolescence, including academic and interpersonal functioning and psychopathology. Rothbart's temperament model is among the most well-studied and supported approaches to adolescent temperament, and contains 3 main components: positive emotionalit

Aβ (beta-amyloid peptide) is an important contributor to Alzheimer's disease (AD). We modeled Aβ toxicity in yeast by directing the peptide to the secretory pathway. A genome-wide screen for toxicity modifiers identified the yeast homolog of phosphatidylinositol binding clathrin assembly protein (PICALM) and other endocytic factors connected to AD whose relationship to Aβ was previously unknown. The factors identified in yeast modified Aβ toxicity in glutamatergic neurons of Caenorhabditis elegans and in primary rat cortical neurons. In yeast, Aβ impaired the endocytic trafficking of a plasma membrane receptor, which was ameliorated by endocytic pathway factors identified in the yeast screen. Thus, links between Aβ, endocytosis, and human AD risk factors can be ascertained with yeast as a model system.

It has been widely accepted that different types of innovation have different implications for the whole innovation process. However, less is known about how the specific type of innovation may affect the entire supply chain. In order to explore how the character of innovations affects supply chain

It has been widely accepted that different types of innovation have different implications for the whole innovation process. However, less is known about how the specific type of innovation may affect the entire supply chain. In order to explore how the character of innovations affects supply chain

Complexes of specific assembly factors and generic endoplasmic reticulum (ER) chaperones collectively called the major histocompatibility complex (MHC) class I peptide loading complex (PLC) function in the folding and assembly of MHC class I molecules. The glycan binding chaperone calreticulin and partner oxidoreductase ERp57 are important in MHC class I assembly, but the sequence of assembly events and specific interactions involved remain incompletely understood. We show that the recruitments of calreticulin and ERp57 to the PLC are co-dependent and also dependent upon the ERp57 binding site and the glycan of the assembly factor tapasin. Furthermore, the ERp57 binding site and the glycan of tapasin enhance β2m and MHC class I heavy chain recruitment to the PLC, with the ERp57 binding site having the dominant effect. On the other hand, the conserved MHC class I heavy chain glycan played a minor role in calreticulin recruitment into the PLC, but impacted the recruitment of heavy chains into the PLC, and glycan-deficient heavy chains were impaired for tapasin-independent and tapasin-assisted assembly. The conserved MHC class I glycan and tapasin facilitated an early step in the assembly of heavy chain-β2m heterodimers, for which tapasin-ERp57 or tapasin-calreticulin complexes were not required. Together, these studies provide insights into how PLCs are constructed, demonstrate two distinct mechanisms by which PLCs can be stabilized, and suggest the presence of intermediate heavy chain-deficient PLCs. PMID:21263072

Grain yield in many cereal crops is largely determined by grain size. Here we report the genetic and molecular characterization of GS3, a major quantitative trait locus for grain size. It functions as a negative regulator of grain size and organ size. The wild-type isoform is composed of four putative domains: a plant-specific organ size regulation (OSR) domain in the N terminus, a transmembrane domain, a tumor necrosis factor receptor/nerve growth factor receptor (TNFR/NGFR) family cysteine-rich domain, and a von Willebrand factor type C (VWFC) in the C terminus. These domains function differentially in grain size regulation. The OSR domain is both necessary and sufficient for functioning as a negative regulator. The wild-type allele corresponds to medium grain. Loss of function of OSR results in long grain. The C-terminal TNFR/NGFR and VWFC domains show an inhibitory effect on the OSR function; loss-of-function mutations of these domains produced very short grain. This study linked the functional domains of the GS3 protein to natural variation of grain size in rice.

An optimized variant of the nested Markov chain Monte Carlo [n(MC)(2)] method [J. Chem. Phys. 130, 164104 (2009)] is applied to fluid N(2). In this implementation of n(MC)(2), isothermal-isobaric (NPT) ensemble sampling on the basis of a pair potential (the "reference" system) is used to enhance the efficiency of sampling based on Perdew-Burke-Ernzerhof density functional theory with a 6-31G(*) basis set (PBE6-31G(*), the "full" system). A long sequence of Monte Carlo steps taken in the reference system is converted into a trial step taken in the full system; for a good choice of reference potential, these trial steps have a high probability of acceptance. Using decorrelated samples drawn from the reference distribution, the pressure and temperature of the full system are varied such that its distribution overlaps maximally with that of the reference system. Optimized pressures and temperatures then serve as input parameters for n(MC)(2) sampling of dense fluid N(2) over a wide range of thermodynamic conditions. The simulation results are combined to construct the Hugoniot of nitrogen fluid, yielding predictions in excellent agreement with experiment.

Full Text Available The viability and functionality of probiotics may be influenced by industrial production processes resulting in a decrease in probiotic efficiency that benefit the health of humans. This study aimed to investigate the probiotic characteristics of Bifidobacterium strains isolated from fecal samples of healthy Thai infants. In the present work, three local strains (BF014, BF052, and BH053 belonging to Bifidobacterium animalis showed a great resistance against conditions simulating the gastrointestinal tract. Among these, B. animalis BF052 possessed considerable probiotic properties, including high acid and bile tolerance, strong adhesion capability to Caco-2 cells, and inhibitory activity against pathogens including Salmonella typhimurium and Vibrio cholerae. This strain also exhibited a high survival rate compared to commercial strains during storage in a wide variety of products, including pasteurized milk, soy milk, drinking yogurt, and orange juice. The impact of food processing processes as well as the freeze-drying process, storage of freeze-dried powders, and incorporation of freeze-dried cells in food matrix on probiotic properties was also determined. The stability of the probiotic properties of the BF052 strain was not affected by food processing chain, especially its resistance in the simulated gastrointestinal conditions and its adherence ability to Caco-2 cells. It indicates that it satisfies the criteria as a potential probiotic and may be used as an effective probiotic starter in food applications.

Pathogenic bacteria cause significant morbidity and mortality to humans. There is a pressing need to establish a simple and reliable method to detect them. Herein, we show that magnetic particles (MPs) can be functionalized by poly(diallyl dimethylammonium chloride) (PDDA), and the particles (PDDA-MPs) can be utilized as adsorbents for capture of pathogenic bacteria from aqueous solution based on electrostatic interaction. The as-prepared PDDA-MPs were characterized by Fourier-transform infrared spectroscopy, zeta potential, vibrating sample magnetometry, X-ray diffraction spectrometry, scanning electron microscopy, and transmission electron microscopy. The adsorption equilibrium time can be achieved in 3min. According to the Langmuir adsorption isotherm, the maximum adsorption capacities for E. coli O157:H7 (Gram-negative bacteria) and L. monocytogenes (Gram-positive bacteria) were calculated to be 1.8×10(9) and 3.1×10(9)cfumg(-1), respectively. The bacteria in spiked mineral water (1000mL) can be completely captured when applying 50mg of PDDA-MPs and an adsorption time of 5min. In addition, PDDA-MPs-based magnetic separation method in combination with polymerase chain reaction and capillary electrophoresis allows for rapid detection of 10(1)cfumL(-1) bacteria.

Full Text Available Medium-chain acyl-CoA dehydrogenase (MCAD deficiency (OMIM 201450 is the most common inherited disorder of fatty acid metabolism presenting with hypoglycaemia, hepatopathy and Reye-like symptoms during catabolism. In the past, the majority of patients carried the prevalent c.985A>G mutation in the ACADM gene. Since the introduction of newborn screening many other mutations with unknown clinical relevance have been identified in asymptomatic newborns. In order to identify functional effects of these mutant genotypes we correlated residual MCAD (OMIM 607008 activities as measured by octanoyl-CoA oxidation in lymphocytes with both genotype and relevant medical reports in 65 newborns harbouring mutant alleles. We identified true disease-causing mutations with residual activities of 0 to 20%. In individuals carrying the c.199T>C or c.127G>A mutation on one allele, residual activities were much higher and in the range of heterozygotes (31%-60%. Therefore, both mutations cannot clearly be associated with a clinical phenotype. This demonstrates a correlation between the octanoyl-CoA oxidation rate in lymphocytes and the clinical outcome. With newborn screening, the natural course of disease is difficult to assess. The octanoyl-CoA oxidation rate, therefore, allows a risk assessment at birth and the identification of new ACADM genotypes associated with asymptomatic disease variants.

We consider a density-functional theory to describe nonuniform fluids composed of chain molecules, containing a charged segment each, and spherical counterions. The chain molecules are modeled as freely jointed chains of hard spheres, the counterions are oppositely charged spheres of the same diameter as all segments of chain molecules. The theory is applied to study the structure of adsorbed layers, the excess adsorption isotherms, the capacitance of the double layer, and the potential of the zero charge. We show that all electric properties are strongly dependent on the length of the chain molecules. Moreover, these properties are also dependent on the position of the charged segment in the chain.

Default-mode network (DMN) functional connectivity and its task-dependent down-regulation have attracted a lot of attention in the field of neuroscience. Nevertheless, the exact underlying mechanisms of DMN functional connectivity, or more specifically, the blood oxygen level-dependent (BOLD) signal, are still not completely understood. To investigate more directly the association between local glucose consumption, local glutamatergic neurotransmission and DMN functional connectivity during rest, the present study combined for the first time 2-Deoxy-2-[18F]fluoroglucose positron emission tomography (FDG-PET), proton magnetic resonance spectroscopy (1H-MRS), and resting-state functional magnetic resonance imaging (rs-fMRI). Seed-based correlation analyses, using a key region of the DMN i.e. the dorsal posterior cingulate cortex as seed, revealed overall striking spatial similarities between fluctuations in FDG-uptake and the BOLD signal. More specifically, a conjunction analysis across both modalities showed that DMN areas as the inferior parietal lobe, angular gyrus, precuneus, middle and medial frontal gyrus were positively correlated with the dorsal posterior cingulate cortex. Furthermore, we could demonstrate that local glucose consumption in the medial frontal gyrus, posterior cingulate cortex and left angular gyrus was associated with functional connectivity within the DMN. We did not find a relationship between glutamatergic neurotransmission and functional connectivity. In line with very recent findings, our results provide further evidence for a close association between local metabolic activity and functional connectivity and enable further insights towards a better understanding of the underlying mechanisms of the BOLD signal.

The T-cell receptor beta (TCRbeta)/pre-TCRalpha (pTalpha) pre-TCR complex (pre-TCR) signals the expansion and differentiation of de-veloping thymocytes. Functional pro-perties of the pre-TCR rely on its unique pTalpha chain, which suggests the participation of specific intracellular adaptors. However, pTalpha-interacting molecules remain unknown. Here, we identified a polyproline-arginine sequence in the human pTalpha cytoplasmic tail that interacted in vitro with SH3 domains of the CIN85/CMS family of adaptors, and mediated the recruitment of multiprotein complexes involving all (CMS, CIN85, and CD2BP3) members. Supporting the physiologic relevance of this interaction, we found that 1 such adaptor, CMS, interacted in vivo with human pTalpha, and its expression was selectively up-regulated during human thymopoiesis in pre-TCR-activated thymocytes. Upon activation, pre-TCR clustering was induced, and CMS and polymerized actin were simultaneously recruited to the pre-TCR activation site. CMS also associated via its C-terminal region to the actin cytoskeleton in the endocytic compartment, where it colocalized with internalized pTalpha in traffic to lysosomal degradation. Notably, deletion of the pTalpha CIN85/CMS-binding motif impaired pre-TCR-mediated Ca(2+) mobilization and NFAT transcriptional activity, and precluded activation induced by overexpression of a CMS-SH3 N-terminal mutant. These results provide the first molecular evidence for a pTalpha intracellular adaptor involved in pre-TCR function.

To describe functional limitations in obese women. Comparisons of functional limitations in obese women and in a normal-weight reference group regarding mobility, balance and housework transport. A large room with a corridor and staircase nearby. Fifty-seven consecutively selected obese female outpatients, mean age 44 y, body mass index (BMI) 37 kg.m(-2), and 22 voluntary references, mean age 49 y, BMI 22 kg.m(-2). Pain questionnaire (for background data); a new valid and reliable test protocol measuring activities of daily life (ADL), pain and exertion, heart rate, balance and speed. The patients had problems in performing 13 of 16 actions compared with the references (P-values between 0.05 and 0.001). They moved more slowly and had difficulties and /or pain and exertion in flexibility tasks, balancing, activities at floor level (bending and kneeling), climbing stairs and carrying groceries. BMI (P=0.002), age (P=0.02) and current pain (P=0.02) from the lower body predicted functional limitation. The functional test reflected functional limitations in obese women, revealing difficulties and perceived pain in ADL. The test protocol can be used to evaluate the effects of training or dieting. For clinical use we recommend considering BMI, age and current pain for use when individualizing advice on training.

It has recently been demonstrated that the use of anion exchange membranes (AEMs) in vanadium redox flow batteries (VRFBs) can reduce the migration of vanadium ions through the membrane due to the Donnan exclusion effect among the positively charged functional groups and vanadium ions. However, AEMs are plagued by low chemical stability in harsh chemical environments. Here we propose and fabricate a pyridinium-functionalized cross-linked AEM for VRFBs. The pyridinium-functionalized bromomethylated poly (2,6-dimethyl-1,4-phenylene oxide) exhibits a superior chemical stability as a result of the strengthened internal cross-linking networks and the chemical inertness of the polymer backbone. Therefore, the membrane exhibits littler decay in a harsh environment for 20 days during the course of an ex situ immersion test. A cycling test also demonstrates that the VRFB assembled with the membrane enable to retain 80% of the initial discharge capacity over 537 cycles with a capacity decay rate of 0.037% cycle-1. Meanwhile, the membrane also shows a low vanadium permeability and a reasonably high conductivity in supporting electrolytes. Hence, all the measurements and performance tests reported in this work suggest that the membrane is a promising AEM for redox flow batteries to achieve excellent cycling stability and superior cell performance.

Cell adhesion represents the most direct way of coordinating synaptic connectivity in the brain. Recent evidence highlights the importance of a trans-synaptic interaction between postsynaptic neuroligins and presynaptic neurexins. These transmembrane molecules bind each other extracellularly to promote adhesion between dendrites and axons. This signals the recruitment of presynaptic and postsynaptic molecules to form a functional synapse. Remarkably, neuroligins alone can induce the formation of fully functional presynaptic terminals in contacting axons. Conversely, neurexins alone can induce postsynaptic differentiation and clustering of receptors in dendrites. Therefore, the neuroligin-neurexin interaction has the unique ability to act as a bi-directional trigger of synapse formation. Here, we review several recent studies that offer clues as to how these proteins form synapses and how they might function in the brain to establish and modify neuronal network properties and cognition.

Our goal is to develop constitutive relations for the behavior of a solid polymer during high-strain-rate deformations. In contrast to the classic thermodynamic techniques for deriving stress-strain response in static (equilibrium) circumstances, we employ a statistical-mechanics approach, in which we evolve a probability distribution function (PDF) for the velocity fluctuations of the repeating units of the chain. We use a Langevin description for the dynamics of a single repeating unit and a Lioville equation to describe the variations of the PDF. Moments of the PDF give the conservation equations for a single polymer chain embedded in other similar chains. To extract single-chain analytical constitutive relations these equations have been solved for representative loading paths. By this process we discover that a measure of nonuniform chainlink displacement serves this purpose very well. We then derive an evolution equation for the descriptor function, with the result being a history-dependent constitutive relation.

Full Text Available It has been conjectured that basic individual differences in attentional control influence higher-level executive functioning and subsequent academic performance in children. The current study sets out to complement the limited body of research on early precursors of executive functions. It provides both a cross-sectional, as well as a longitudinal exploration of the relationship between executive functions and more basic attentional control mechanisms, assessed via children’s performance on memory storage tasks, and influenced by individual differences in anxiety. Multiple measures of verbal and visuospatial short-term memory (STM were administered to children between 3 and 6 years old, alongside a nonverbal measure of intelligence, and a parental report of anxiety symptoms. After 9 months, children were re-tested on the same STM measures, at which time we also administered multiple measures of executive functioning: verbal and visuospatial working memory (WM, inhibition, and shifting. A cross-sectional view of STM development indicated that between 3 and 6 years the trajectory of visuospatial STM and executive functions underwent a gradual linear improvement. However, between 5 and 6 years progress in verbal STM performance stagnated. Hierarchical regression models revealed that trait anxiety was negatively associated with WM and shifting, while nonverbal intelligence was positively related to WM span. When age, gender, nonverbal intelligence, and anxiety were controlled for, STM (measured at the first assessment was a very good predictor of overall executive performance. The models were most successful in predicting WM, followed by shifting, yet poorly predicted inhibition measures. Further longitudinal research is needed to directly address the contribution of attentional control mechanisms to emerging executive functioning and to the development of problematic behavior during early development.

The THO complex is involved in transcription, genome stability, and messenger ribonucleoprotein (mRNP) formation, but its precise molecular function remains enigmatic. Under heat shock conditions, THO mutants accumulate large protein-DNA complexes that alter the chromatin density of target genes...... (heavy chromatin), defining a specific biochemical facet of THO function and a powerful tool of analysis. Here, we show that heavy chromatin distribution is dictated by gene boundaries and that the gene promoter is necessary and sufficient to convey THO sensitivity in these conditions. Single...

Full Text Available The relationship between a functional assessment-based parent intervention and preschoolers' challenging behaviors was examined in the current study. A single subject design with a multiple baseline across 2 parent-child dyads was implemented. The researchers collaborated with parents to design the FA-based interventions and parents received varying levels of support throughout the study. Results indicate that parents were able to implement the functional assessment-based interventions, and these interventions effectively reduced children's challenging behaviors. In addition, parents continued implementing the intervention strategies following termination of the intervention, and children's challenging behaviors remained low.

Full Text Available Thermally induced shape-memory effect (SME in tensile mode was investigated in binary and ternary blends of two ethylene-1-octene copolymers with a degree of branching of 30 and 60 CH3/1000C and/or nearly linear polyethylene cross-linked after melt mixing with 2 wt% of liquid peroxide 2,5-dimethyl-2,5-di-(tert.butylperoxy-hexane at 190°C. The average cross-link density estimated by means of the Mooney-Rivlin equation on the basis of tensile test data was characterized between 130 and 170 mol•m–3 depending on the blend composition. Thermal analysis points out multiple crystallization and melting behavior of blends caused by the existence of several polyethylene crystal populations with different perfection, size and correspondingly different melting temperature of crystallites. That agrees well with the diversity of blends phase morphology characterized by atomic force microscopy. However, triple- and quadruple-SME could be observed only after two- and accordingly three-step programming of binary and tertiary blends, respectively, at suitable temperatures and strains. Compared to performances obtained for the same blend after single-step programming above the maximal melting temperature the significantly poorer characteristics of SME like strain fixity and strain recovery ratio as well as recovery strain rate occurred after multi-step programming.

Mefenamic acid (MFA), a carboxylic acid–containing nonsteroidal anti-inflammatory drug, is metabolized into the chemically-reactive MFA-1-O-acyl-glucuronide (MFA-1-O-G), MFA-acyl-adenylate (MFA-AMP), and the MFA-S-acyl-coenzyme A (MFA-CoA), all of which are electrophilic and capable of acylating nucleophilic sites on biomolecules. In this study, we investigate the nonenzymatic ability of each MFA acyl-linked metabolite to transacylate amino and thiol functional groups on the acceptor biomolec...

Full Text Available We show some symmetry relations among the correlation functions of the integrable higher-spin XXX and XXZ spin chains, where we explicitly evaluate the multiple integrals representing the one-point functions in the spin-1 case. We review the multiple-integral representations of correlation functions for the integrable higher-spin XXZ chains derived in a region of the massless regime including the anti-ferromagnetic point. Here we make use of the gauge transformations between the symmetric and asymmetric R-matrices, which correspond to the principal and homogeneous gradings, respectively, and we send the inhomogeneous parameters to the set of complete 2s-strings. We also give a numerical support for the analytical expression of the one-point functions in the spin-1 case.

In this work, aminopropylmethylpolysiloxane (AMS) functionalized luminescent carbon dots (AMS-CDs) were prepared via a one-step solvothermal method. AMS-CDs could be self- or co-cross-linking with AMS to form 3D flexible transparent silicone rubbers (SRs) where CDs acted as cross-linking points, so the loading fraction of AMS-CDs could be adjusted from 10 to 100 wt %, thus modulating fluorescence properties and flexibility of silicone rubbers. Because of the self-curing property and high thermal stability, AMS-CDs were also studied in white LEDs (WLEDs), serving as a color conversion and encapsulation layer of GaN based blue LEDs simultaneously that would avoid the traditional problem of poor compatibility between emitting and packaging materials. And the color coordinate of AMS-CDs based WLEDs (0.33, 0.28) was very close to the pure white light. In addition, the obtained CDs cross-linked SRs had good transparency (T > 80%) at 510-1400 nm and high refractive indexes (1.33-1.54) that could meet the need of commercial packaging materials and optical application. AMS-CDs were also promising to be used in the UV LEDs based WLEDs according to their wide wavelength emission and flexible optoelectronic device.

The quantification or estimation of the economic and non-economic values of ecosystem services can be done from a number of distinct approaches. For example, practitioners may use ecosystem services production function models (ESPFMs) for a particular location, or alternatively, ...

Adolescents' somatisation (i.e., the psychological tendency to experience and report multiple physical complaints for which no definite medical cause can be found; SOM) and functional impairment (i.e., all bothersome aftermath of somatisation; FI) were studied in relation to mothers' protection, enc

To elucidate how obsessional symptoms might develop or intensify in late-life, we tested a risk model. We posited that cognitive self-consciousness (CSC), a tendency to be aware of and monitor thinking, would increase reactivity to aging-related cognitive changes and mediate the relationship between cognitive functioning and obsessive-compulsive disorder (OCD) symptoms. Older adults (Mage = 76.7 years) completed the Dementia Rating Scale-2 (DRS-2), a CSC measure, and an OCD symptom measure up to four times over 18 months. A model that included DRS-2 age and education adjusted total score as the indicator of cognitive functioning fit the data well, and CSC score change mediated the relationship between initial cognitive functioning and changes in OCD symptoms. In tests of a model that included DRS-2 Initiation/Perseveration (I/P) and Conceptualization subscale scores, the model again fit the data well. Conceptualization scores, but not I/P scores, were related to later OCD symptoms, and change in CSC scores again mediated the relationship. Lower scores on initial cognitive functioning measures predicted increases in CSC scores over time, which in turn predicted increases in OCD symptoms over the 18 months of the study. Implications for understanding late-life obsessional problems are discussed.